ТЕРАПЕВТИЧЕСКИЙ ПРЕПАРАТ ДЛЯ ЛЕЧЕНИЯ НЕЙРОДЕГЕНЕРАТИВНЫХ ЗАБОЛЕВАНИЙ И ЕГО ПРИМЕНЕНИЕ

Группа изобретений относится к области фармацевтики, а именно к новым терапевтическим препаратам для лечения нейродегенеративных заболеваний, их получению и применению. Предложено соединение формулы I, а также применение соединения формулы I для получения лекарственного средства для профилактики, облегчения или лечения нейродегенеративных заболеваний или депрессии, и фармацевтическая композиция, содержащая указанное соединение и фармацевтически приемлемый носитель. Предложен также способ профилактики, облегчения или лечения нейродегенеративных заболеваний или депрессии, включающий введение субъекту, нуждающемуся в этом, эффективного количества соединения формулы I или его фармацевтически приемлемой соли, в частности, соединения II, III, IV или V. Предложены также способы получения соединений III, IV или V. Показано, что соединение формулы I может эффективно усиливать функционирование нервных стволовых клеток как в in vivo, так и in vitro экспериментах, и может быть применено в рамках лечебного ...

СОЕДИНЕНИЕ САХАРА

Изобретение относится к химической и биотехнологической промышленности. Соединение сахара получено путем воздействия на фукоидан эндофукоиданлиазы. Данное соединение обладает биологической активностью и его применение позволяет анализировать структуру фукоидана. 9 з.п. ф-лы, 42 ил., 2 табл.

ПРОИЗВОДНЫЕ ГЕМЦИТАБИНА

Изобретение относится к производным гемцитабина формулы (I), где R1, R2, R3 независимо выбирают из водорода и C18 и С20 насыщенных и мононенасыщенных ацильных групп, при условии, что R1, R2, R3 не могут все быть водородом. Соединения по изобретению обладают противораковой активностью и могут входить в состав фармацевтической композиции с аналогичным назначением. Также предлагается способ получения производных гемцитабина, включающий взаимодействие гемцитабина с производным мононенасыщенной С18 или С20 жирной кислоты FaX, где Х представляет собой удаляемую группу, a Fa является ацильным остатком указанной кислоты. 3 с. и 8 з.п.ф-лы, 7 табл.

ВОДОРАСТВОРИМЫЕ ПОРОШКИ И ТАБЛЕТКИ

Изобретение может быть использовано в фармацевтике и пищевой промышленности при изготовлении растворимых или диспергируемых в воде порошков или таблеток на углеводной основе. Углеводная матрица состоит, по крайней мере, на 90% из углевода, например крахмала или сахара. Порошок или таблетку со скрытой пористостью обрабатывают газом так, чтобы содержащийся в порах газ усиливал растворение или диспергирование при контакте с водой. Газом является азот, диоксид углерода, воздух, кислород, гелий, водород, аргон, неон, метан, этан, криптон, хлор, хлорфторуглерод или их смесь. Газ вводят преимущественно под давлением при температуре выше Tg углевода. Порошок или таблетка может дополнительно содержать белок, гидроколлоид или жир и не образует пену при растворении или диспергировании. 5 н. 30 з.п. ф-лы, 1 ил., 2 табл.

СПОСОБ ПОЛУЧЕНИЯ МАКРОЦИКЛИЧЕСКОГО ЛАКТОНА

Изобретение относится к органической химии, в частности к способам получения соединения формулы (I): в которой m означает 0, 1 или 2; n означает 0, 1, 2 или 3 и А обозначает двойную связь, В обозначает двойную или простую связь, С обозначает двойную связь, D обозначает простую связь, Е и F обозначают двойную связь; r1 обозначает Н или С1-С8алкил; r2 обозначает Н, С1 -С8алкил или ОН; R3 и R4 каждый независимо друг от друга обозначают H или С1-С8алкил; R5 обозначает Н или С1 -С8 алкил; R6 обозначает Н; R7 обозначает ОН; R8 и R9 независимо друг от друга обозначают Н или С1-С10алкил; в свободной форме или в виде соли, заключающийся в том, что соединение формулы (II): вводят в контакт с биокатализатором, который способен избирательно окислять спирт в положении 4", с получением соединения формулы (III): в которых R1-R7, m, n, А, В, С, D, Е и F имеют те же значения, что и указанные выше для формулы (I), и соединение формулы (III) подвергают взаимодействию в присутствии восстановителя с известным ...

СИНТЕЗ β-L-2'-ДЕЗОКСИНУКЛЕОЗИДОВ

Изобретение относится к способу получения 2'-дезокси-β-L-тимидина, включающему взаимодействие 5'-O-тритил- или 5'-O-диметокситритил-защищенного 2,2'-ангидро-1-β-L-арабинофуранозилтимина с восстановителем RedAl и комплексообразующим агентом 15-краун-5-эфиром в полярном растворителе 1,2-диметоксиэтане (DME) или тетрагидрофуране (ТГФ) с получением 5'-O-тритил- или 5'-O-диметокситритил-защищенного 2'-дезокси-(3-L-тимидина, подвергающегося при необходимости удалению защиты. Изобретение относится также к способу получения 2'-дезокси-(3-L-тимидина, включающему взаимодействие L-арабинозы с цианамидом с последующим взаимодействием промежуточного продукта - L-арабинофуранозиламинооксазолина - с циклизующим или конденсирующим агентом с образованием 2,2'-ангидро-1-(3-L-арабинофуранозилтимина; взаимодействие последнего с восстановителем RedAl и комплексообразующим агентом 15-краун-5-эфиром в полярном растворителе 1,2-диметоксиэтане (DME) или тетрагидрофуране (ТГФ) с получением 2'-дезокси-β-L-тимидина ...

СПОСОБЫ ХИМИЧЕСКОГО СИНТЕЗА ФИЛЛИРИНА

Изобретение относится к способу химического синтеза филлирина, который может быть применен в химической промышленности. Предложенный способ включает следующие этапы: (1) растворение акцептора гликозила - филлигенина и донора гликозила - 2,3,4,6-тетра-О-ацил-D-глюкопиранозил трихлорацетимидата в атмосфере инертного газа при добавлении катализатора и молекулярного сита в безводном дихлорметане или безводном трихлорметане для гликозилирования с получением тетраацил-филлирина, (2) растворение тетраацил-филлирина в органическом растворителе, добавление метоксида натрия для деацилирования, добавление кислотного регулятора рН для доведения значения рН реакционной смеси до нейтрального и проведение очистки для получения филлирина. Предложен новый эффективный способ химического синтеза филлирина. 5 з.п. ф-лы, 5 табл., 4 пр.

СПОСОБ ФТОРИРОВАНИЯ ДЛЯ СИНТЕЗА 2-[18F]-ФТОР-2-ДЕЗОКСИ-D-ГЛЮКОЗЫ

Изобретение относится к способу получения защищенного фторированного производного глюкозы, включающему взаимодействие производного тетраацетилманнозы с фторидом, отличающемуся тем, что реакцию проводят в растворителе, содержащем воду в количестве, превышающем 1000 частей на миллион и составляющем менее 50000 частей на миллион. Предпочтительно защищенное фторированное производное глюкозы представляет собой 2-фтор-1,3,4,6-тетра-O-ацетил-D-глюкозу (тетраацетилфторглюкозу или pFDG), производное тетраацетилманнозы представляет собой 1,3,4,6-тетра-O-ацетил-2-O-трифторметансульфонил-β-D-маннопиранозу (трифлат тетраацетилманнозы), растворитель представляет собой ацетонитрил, фторид представляет собой ионный фторид с калиевым противоионом и к фториду добавлен катализатор фазового переноса, такой как 4,7,13,16,21,24-гексаокса-1,10-диазабицикло-[8,8,8]-гексакозан. 13 з.п. ф-лы, 2 табл., 3 ил.

НОВЫЕ ДИМЕРЫ ПРОИЗВОДНЫХ ЦИТИДИНА И ИХ ПРИМЕНЕНИЯ

Настоящее изобретение относится к димеру производного цитидина формулы (I), его применению для получения противоопухолевого средства, фармацевтическим композициям на его основе и способу его получения, которые могут применяться в медицине и фармацевтической промышленности(I),где R1 и R2 независимо представляют собой C-алкил или -(CH)-Ph; R3 представляет собой водород или C-алкоксикарбонил; R4 представляет собой водород или C-алкоксикарбонил; R5 представляет собой -(CH)-. Способ включает получение соединений формул (II) и (III), превращение соединения формулы (II) в соединение формулы (IV) и реакцию соединений (IV) и (III) с получением димера формулы (I)(II)(III)(IV)Предложены новые соединения, эффективные для лечения злокачественных солидных опухолей, фармацевтические композиции на их основе и эффективный способ их получения. 4 н. и 4 з.п. ф-лы, 4 пр., 9 табл., 6 ил.

СПОСОБ ПОЛУЧЕНИЯ СОЛЕЙ 5'-ТРИФОСФАТОВ ПРИРОДНЫХ И МОДИФИЦИРОВАННЫХ ДЕЗОКСИРИБО- И РИБООЛИГОНУКЛЕОТИДОВ

Изобретение относится к способу получения солей 5'-трифосфатов природных и модифицированных дезокси- и рибоолигонуклеотидов, заключающемуся в том, что исходный реагент - защищенный природный или модифицированный олигонуклеотид, дезокси- или риборяда, в виде 0,1-0,05 М раствора, монофосфорилируют в пиридине 2-3-кратным избытком хлорокиси фосфора в течение 10-15 минут, далее полученное активированное производное олигонуклеотида обрабатывают 10-15-кратным избытком раствора бис-трибутиламмонийной соли пирофосфата в ацетонитриле и 20-кратным избытком третичного амина и выдерживают реакционную смесь в течение 15-30 минут с последующим разложением промежуточного триметафосфатного производного олигонуклеотида триэтиламмонийбикарбонатным буфером, очисткой целевого продукта с помощью обращенно-фазовой хроматографии (ОФХ), удалением защитных групп с функциональных групп олигонуклеотида и повторной очисткой целевого продукта с помощью ОФХ. Выходы целевых продуктов после очистки составляют 45-92%. Чистота ...

СПОСОБ ПОЛУЧЕНИЯ ГЛИКОЗИДА КУРКУЛИГОЗИДА А

Изобретение относится к органической химии. Предложен способ получения гликозида куркулигозида А, заключающийся в том, что в колбу помещают толуол, добавляют 5-гидроксисалициловый альдегид и растворяют в толуоле, затем добавляют 4-диметиламинопиридин в уксусном ангидриде, после чего полученную реакционную массу перемешивают при комнатной температуре с получением 5-ацетилоксисалицилового альдегида, который затем помещают в колбу вместе с оксидом серебра (I) и ацетобромглюкозой, растворяют в хинолине и перемешивают при комнатной температуре в течение 2 часов с получением 5-(ацетилокси)-2-[(2,3,4,6-тетра-O-ацетил-β-D-глюкопиранозил)окси]бензальдегида, который растворяют в этилацетате, добавляют борогидрид натрия и перемешивают при комнатной температуре с получением 5-(ацетилокси)-2-(гидроксиметил)фенил-(2,3,4,6-тетра-O-ацетил)-β-D-глюкопиранозида, который далее вместе с тетрабромметаном растворяют в этилацетате в среде аргона, а затем добавляют трифенилфосфин, перемешивают при комнатной температуре ...

СПОСОБЫ ВОДНОГО ДЕАЦИЛИРОВАНИЯ, СТАБИЛИЗИРОВАННОГО БУФЕРОМ

... 1. Способ получения сукралозы из подаваемой смеси, содержащей соединение ацил-сукралозы в водном растворе, предусматривающий (а) доведение рН указанной подаваемой смеси до значения в диапазоне от 8,0 до 12,0; (b) выдерживание указанной подаваемой смеси при подходящей температуре в течение времени, достаточного для эффективного превращения указанного соединения ацил-сукралозы в свободную сукралозу; (с) добавление буфера к указанной подаваемой смеси в количестве, достаточном для стабилизации указанного рН в указанном диапазоне на протяжении указанной стадии выдерживания; (d) снижение указанного рН указанной подаваемой смеси до значения от примерно 4 до примерно 8; (е) выделение сукралозы из продукта стадии (d), с получением таким образом выделенной сукралозы. 2. Способ по п.1, где указанное значение рН составляет примерно 10,5. 3. Способ по п.1, где указанный буфер выбирают из группы, состоящей из аминов, аминокислот, фенолов, неорганических кислот, сахарина, ксантина, гидрохинина и их смесей ...

ФУНКЦИОНАЛИЗИРОВАННЫЕ БЕТА 1,6 ГЛЮКОЗАМИН-ДИСАХАРИДЫ И СПОСОБ ИХ ПОЛУЧЕНИЯ

... 1. Способ получения асимметрично или симметрично замещенных β-(1→6)-связанных глюкозамин-дисахаридов, включающий реакцию соединения формулы 10: ! ! в которой ! R1 представляет собой группу, выбранную из (C3-C6)алкенила, такого как C3 или С4алкенил, предпочтительно 2-пропенил или 1-пропенил; ! X представляет водород, группу, выбранную из бензила или замещенного бензила, такого как 4-метоксибензил или 3,4-диметоксибензил, или 2,5-диметоксибензил, или 2,3,4-триметоксибензил, или 3,4,5-триметоксибензил; ! R0 выбран из R5 или R2, где R5 выбран из ! (i) ацильной группы, происходящей из карбоновой кислоты с линейной цепью, имеющей от 2 до 24 атомов углерода, предпочтительно гидроксиацильной группы, такой как 3-гидроксиацильная группа, оксоацильной группы, такой как 3-оксоацильная группа, аминоацильной группы, такой как 3-аминоацильная группа; ! (ii) ацилоксиацильной группы, предпочтительно 3-ацилоксиацильной группы, ациламиноацильной группы, предпочтительно 3-ациламиноацильной группы, ацилтиоацильной ...

Способ получения бутилполиглюкозида водного раствора

Изобретение относится к способу получения бутилполиглюкозида где n=1-3, включающему взаимодействие глюкозы с бутиловым спиртом при соотношении 1:6 моль в присутствии катализатора n-толуолсульфокислоты в количестве 0,2-0,3 мас.%, с последующей отгонкой части бутанола, добавлением к реакционной массе бутанола, нейтрализацией реакционной массы гидроксидом натрия и отгонкой избытка спирта, отличающийся тем, что на стадии отгонки избытка спирта к реакционной массе добавляют воду и отгоняют азеотропную смесь. Технический результат: разработан новый способ получения бутилполиглюкозида - неионогенного поверхностно-активного вещества непосредственно в водном растворе с высокой массовой долей основного вещества. 2 пр.

СПОСОБ СИНТЕЗА В РАСТВОРЕ МАКРОМОЛЕКУЛ ИЗ ЗВЕНЬЕВ ПРОИЗВОДНЫХ УГЛЕВОДОВ

Изобретение относится к синтезу макромолекул, состоящих из моносахаридных или олигосахаридных звеньев. Предложен способ синтеза макромолекул, состоящих из звеньев, представляющих собой моносахариды или производные моносахаридов, путём последовательного удлинения цепи на мономер или олигомер, обладающий по меньшей мере двумя функциональными группами, где на первой стадии происходит заякоривание мономера или концевого звена олигомера якорной молекулой с последующим удалением защитной группы, оставляя свободную функциональную группу, к которой затем присоединяется второй мономер или олигомер, который может содержать свободную функциональную группу, защищённую защитной группой, при этом указанная якорная молекула содержит полиолефиновую цепь, или полиолефиновый олигомер, или полиалкен с по меньшей мере от 10 до 50 мономерными звеньями, указанная полиолефиновая цепь представляет собой разветвленную цепь и предпочтительно полиизобутеновую цепь; а также применение указанного способа для синтеза ...

Водное фракционирование биомассы, основанное на новых видах кинетики углеводородного гидролиза

... 1. Многофункциональный способ гидролиза и фракционирования лигноцеллюлозной биомассы, проводимого с целью отделения лигноцеллюлозных сахаров от других компонентов биомассы, содержащей экстрактивные вещества и протеины, часть растворенного лигнина, целлюлозу, глюкозу, полученную из целлюлозы, и растворимый лигнин из указанной биомассы, отличающийся тем, что предусматривает: а) введение в реактор или твердой свежей биомассы, или частично фракционированного материала из лигноцеллюлозной биомассы, содержащих захваченную ими воду или кислоту при рН<5,0, и нагрев до температуры от приблизительно 185°С до приблизительно 205°С; б) обеспечение возможности протекания реакции до точки, в которой приблизительно 60% гемицеллюлозы гидролизовалось, в случае только воды в течение приблизительно 6-10 мин или в случае, когда присутствует кислота, в течение приблизительно 5-10 мин для полного растворения; в) добавление разбавленной кислой жидкости при рН ниже приблизительно 5,0 при температуре с верхним пределом ...

КОМПЛЕКСНЫЕ СОЕДИНЕНИЯ ЖЕЛЕЗА ДЛЯ ТЕРАПЕВТИЧЕСКОГО ПРИМЕНЕНИЯ

Настоящее изобретение относится к способу получения комплексных соединений железа. Предложенный способ включает стадии: (i) предоставления препарата железа, содержащего железо, в форме, выбранной из растворимой в воде соли железа, гидроксида железа или оксида-гидроксида железа, где количество мышьяка в препарате железа не превышает 4,5 мкг на г железа и количество свинца в препарате железа не превышает 1,5 мкг на г железа; и (ii) приведения в контакт препарата железа с углеводным лигандом в присутствии воды с получением комплексного соединения железо-углевод. Технический результат заключается в предоставлении способа получения продуктов железа, которые являются безопасными для введения человеку и сельскохозяйственным животным, а также для людей, употребляющих пищу, являющуюся продуктом животноводства. 10 з.п. ф-лы, 1 табл., 4 пр.

СПОСОБ ПОЛУЧЕНИЯ ДИОСМИНА

Настоящее изобретение относится к области органической химии, конкретно к технологии получения диосмина, который используют при лечении хронической венозной недостаточности и геморроя. Способ получения диосмина включает ацетилирование гесперидина, окисление ацетилированного гесперидина до ацетилированного диосмина донором йода при температуре от 90 до 120°С, кипячение ацетилированного диосмина со спиртом в присутствии основания в автоклаве с обратным холодильником при давлении от 5 до 8 бар. Затем снимают защиту с ацетилированного диосмина для получения диосмина путем нагревания в присутствии основания, выбранного из гидроксида натрия, калия или лития, карбоната калия, метилата натрия или этилата натрия, отдельно или в смеси с ацетатом натрия или калия. На последнем этапе проводят последовательную очистку диосмина обработкой основанием и кислотой. Техническим результатом изобретения является уменьшение содержания примесей 6-йододиосмина и изороифолина в полученном целевом соединении и предоставление ...

Способ получения алкиловых эфиров сахароаскорбиновой кислоты

Изобретение касается Сахаров и, в частности , получения алкиловых эфиров сахароаскорбиновой кислоты общей Формулы Ri-0-C(0)-C-CН (-v ОРз)-СН-О-С(О)- C(OR2) С-О-СНа-СеНб, где RI - фенил, 4-метоксифенил, С1 С18-алкил; R2 - Н или бензил; Нз - Н или ацетил, которые, как промежуточные продукты, могут быть использованы для синтеза активных веществ с антиокислительным действием. Цель изобретения - создание новых полупродуктов указанного назначения. Синтез ведут этери- фикацией сахароаскорбиновой кислоты соответствующим Ri-спиртом. Новые вещества получают с хорошим выходом (до 93%). k ...

Verfahren zur Herstellung von Trehalosederivaten

Kationische, ungesättigte Saccharide sowie daraus hergestellte Polymerisate und deren Verwendung

VERFAHREN ZUM ANHEFTEN VON EINER AKTIVEN METHYLENVERBINDUNG AN KOHLENHYDRAT

GEMCITABIN-DERIVATE

Verfahren zur Herstellung von Aldobionsäureamid

VERFAHREN ZUR HERSTELLUNG VON KOHLENHYDRATPARTIALESTERN

PHARMAZEUTISCHE ZUSAMMENSETZUNGEN MIT OLIGOSACCHARIDEN UND DEREN HERSTELLUNG

VERFAHREN ZUR HERSTELLUNG VON AMINOVERBINDUNGEN AUS HYDROXYLVERBINDUNGEN

A process for the production of amino compounds from hydroxyl compounds (Voelter reaction), according to which a hydroxyl compound is converted with trifluormethanesulphonic acid anhydride in water-free conditions, the corresponding triflate derivative is converted, in water-free conditions, with ammonia or an amine in an organic solvent and the amino compound obtained (formula I) is isolated.

VERFAHREN ZUR HERSTELLUNG VIELKETTIGE POLYPEPTIDE ODER PROTEINE.

Verfahren zum Nachweis, Identifizieren und Quantifizieren von Organismen und Viren

Herstellung heterodimirer menschlicher Fruchtbarkeitshormone

DERIVATISIERTE REDUZIERTE MALTO-OLIGOSACCHARIDE

Verfahren zur Decarboxylierung von 2-Ketoaldonisch-Säuren

POLYMERISABLE DERIVATIVES

PREPARATION OF FLOURO-COMPOUNDS

Association product of alpha-glycosyl alpha, alpha-trehalose with ionic metal compound

An association product of a -glycosyl a , a -treholose with an ionic metal compound; a method for preparing the association product; and a use thereof. The above association product is a preparation of an ionic metal compound which is improved in properties such as deliquescence, reducing power, oxidizing power and slight solubility in water, which are not desirable for the industrial use thereof and are inherent in the ionic metal compound.

Enzymatic production of sucrose-6-ester, an intermediate for the manufacture of halo sugars

A novel process is described for production of 6-acyl-sucrose comprising enzymatic acylation of sucrose by an esterifying agent including an organic acid in presence of a lipase or an esterase in a solvent in which the enzyme used is stable. Chlorinated sucrose, the high intensity sweetener trichlorogalactosucrose can be prepared by chlorination and deacylation of 6-acyl sucrose prepared by the process of this invention.

MANUFACTURE OF SUGAR ESTERS

The invention relates to an improved process for the synthesis of sugar esters carried out in a substantially anhydrous system and in the presence of an organic acid chloride. Any of the known available sugars may be used and in particular hydrolyzate sugars derived from starch are effectively employed in accordance with the present invention to produce sugar esters having superior emulsifying characteristics for use as an ingredient in food products for human consumption.

C5 or C6 monosaccharide-(E)-3(furan-2-yl)monoacrylates, their preparation methods and uses thereof

Controlled degradation of phosphoric acid links in deoxyribose nucleic acid

Controlled degradation of some of the phosphoric acid links of deoxyribose nucleic acid (D.N.A.), some of the phosphoric acid links of which are in the salt form and the remainder of which are in the acid form, is effected by reacting with an alkylating or acylating agent in order to convert either the free phosphoric acid links or the links in salt form into fully esterified phosphoric acid links and subjecting the product so obtained to hydrolysis under mild conditions, whereby cleavage takes place at the fully esterified phosphoric acid links Alkylating agents containing the diazo group convert the secondary phosphate esters in the acid form without altering those in the salt form, while sulphuric ester alkylating agents convert the salt form, leaving the free acids unaltered. The preferred embodiment, in the example, employs a diazo compound, e.g. phenyl diazomethane, or especially diazomethane. The hydrolysis may be effected in either acidic or alkaline aqueous medium, neutral conditions ...

A tetrachlororaffinose and its use in the preparation of sucralose

The novel chlorinated sugar O- alpha -D-6-chloro-6-deoxygalactopyranosyl-(1->6)- alpha -D-4-chloro-4-deoxygalactopyranosyl-(1->2)- beta -D-1, 6-dichloro-1, 6-dideoxyfructofuranoside (TCR) can be used to prepare sucralose by incubating the TCR in solution in the presence of an enzyme serving to remove the 6-chloro-6-deoxygalactosyl moiety from the 6-position, especially an enzyme derived from a strain of Mortierella vinacea, Circinella muscae or Aspergillus niger. TCR is prepared by treating raffinose with thionyl chloride in the presence of triphenylphosphine oxide.

PREPARATION OF D-MANNITOL

Methods for the preparation of diasteromerically pure phosphoramidate prodrugs

Saccharides and saccharide compositions and mixtures

Composition comprising an amorphous non-crystalline glass form of azithromycin.

Method for preparing main hydrolysate by hydrolizing plant cellulose materials with concentrated sulfuric acid

Ethanolate of azithromycin, process for manufacure, and pharmaceutical compositions thereof.

A novel, non-hygroscopic form of azithromycin is disclosed, as well as a method for preparing it by the gradual crystallization of azithromycin from ethanol by the addition of a minimal amount of water to effect crystal formation. Pharmaceutical compositions containing this novel form of azithromycin are also disclosed.

Ethanolate of zithromycin process for manufacture and pharmaceutical compositions thereof

Method for preparing main hydrolysate by hydrolyzing plant cellulose materials with concentrated sulfuric acid

Saccharides and saccharide compositions and mixtures

Methods for the preparation of diasteromerically pure phosphoramidate prodrugs

Process of treatment of aqueous juice sweetened in order to separate and select saccharides with ketonic function.

Composition comprising an amorphous non-crystalline glass form of azithromycin.

Ethanolate of zithromycin process for manufacture and pharmaceutical compositions thereof

Composition comprising an amorphous non-crystalline glass form of azithromycin.

Methods for the preparation of diasteromerically pure phosphoramidate prodrugs

Method for preparing main hydrolysate by hydrolyzing plant cellulose materials with concentrated sulfuric acid

Ethanolate of zithromycin process for manufacture and pharmaceutical compositions thereof

Saccharides and saccharide compositions and mixtures

Method for preparing main hydrolysate by hydrolyzing plant cellulose materials with concentrated sulfuric acid

ALKALINE CERAMIDASE (E.C. 3.5.1.23) CODING GENE OUT PSEUDOMONAS AERUGINOSA

ISOLATION OF NUCLEIC ACIDS USING A POLYKATIONI POLYMER AS FÄLLUNGSMITTEL

LOW ALKYL ESTER FEEDBACK IN THE SYNTHESIS OF POLYOLE FATTY ACID POLYESTERS

FONDAPARINUX SODIUM COMPOSITION OF HIGH PURITY

INSULATING GUM OPERON FROM XYLLELA FASTIDIOSA, ISOLATED NUCLEIC ACID MOLECULES AND THEIR USES

ELEKTROPHORETI SEPARATION FROM NUCLEIC ACIDS FROM BIOLOGICAL SAMPLES AT LOW PH VALUE

PROCEDURE FOR THE PRODUCTION OF CRYSTALLINE MALTIT

PROCEDURE FOR THE PRODUCTION OF NEW AMINOZUCKER - DERIVATIVES

2-SUBSTITUIERTE of ADENOSINE WITH a2 RECEPTOR AFFINITY

ENZYMATIC SYNTHESIS OF OLIGONUKLEOTIDEN

PROCEDURES FOR the PRODUCTION OF 6-O-ALKENYL SUBSITUTIERTEN ERYTHROMYCIN DERIVATIVES

USE OF LAMINARIN IN THE TREATMENT OF CANCER

SUGAR CONNECTIONS

VERFAHREN UND SYSTEM ZUR SYNTHESE VON KOHLENHYDRATEN AUS CO2

TIFF 00000014.TIF 294 208 TIFF 00000015.TIF 294 208 ...

PROCEDURE FOR THE PRODUCTION OF SUCRALOSE BY CHLORINATION OF SUGAR WITH TRI PHOSGENE (BTC)

PROCEDURE FOR THE PRODUCTION OF TRIVALENT IRON COMPLEXES WITH MONO, DIUND OF POLYSACCHARIDZUCKER

PROCEDURE FOR THE CLEANING OF RAW ONE DAUNORUBICIN, DOCORUBICIN AND THEIR ANALOGUES

PROCEDURE FOR THE PRODUCTION OF RADIOIODIERTEM PYRIMIDIN.

COMPOSITION FOR THE THERAPEUTIC OR DIAGNOSTIC USE.

PROCEDURE FOR THE PRODUCTION OF 1,1 ' - DIACETALEN.

(MET-1, DES-CYS1, DES-TYR2, DES-CYS3) HUMAN GAMMA INTERFERON AND BUT CODING DNSSEQUENZ.

PRODUCTION OF 7-HALO-7-DEOXYLINCOMYCINEN.

PRODUCTION OF NUCLEOSIDES.

PRODUCTION AND USE OF A REACTION PRODUCT OF ASCORBIC ACID WITH ALPHA, BETA-INSATIATED KETON OR VINYLALIPHATI KETON.

FSH.

PROCEDURE FOR THE PRODUCTION OF LACTULOSE FROM LACTOSE THROUGH EPIMERISATION WITH SODIUM ALUMINATE.

PROCEDURE FOR THE PRODUCTION VIELKETTIGE POLYPEPTIDE OR PROTEINS.

PROCEDURE FOR THE CHEMICAL OR ENZYMATIC TRANSFORMATION OF A ALDOSE OR A ALDOSEDERIVATES IN AN APPROPRIATE KETOSE OR AN APPROPRIATE KETOSEDERIVAT

STEREOREGULARE POLYNUKLEOTIDEN CONNECTION OF POLYMERS.

PRODUCTION OF HETERODIMERER OF HUMAN OF FERTILITY HORMONES.

PROCEDURE FOR THE CHROMATOGRAPHI SEPARATION FROM MANNIT AND SORBIT

D-MANNOSEODER XYLITO ESTER AND THEIR VERWENUNG THAN DRUGS

PROCEDURE FOR THE PRODUCTION OF RHAMNOSE FROM RHAMNOLIPIDEN.

3 ' - AZIDO-2',3' DIDEOXYURIDIN ANTI- RETROVIRALE COMPOSITION.

PRODUCTION AND EXPRESSION LARGE STRUCTURAL GENES.

A GAMMA INTERFERON CODING SYNTHETIC GENE.

PROCEDURE FOR THE PRODUCTION OF BUTYLOLIGOGLYCOSIDEN.

PHOSPHORYLATION MEANS, PROCEDURE FOR ITS PRODUCTION, PROCEDURE FOR THE PHOSPHORYLATION OF AN ORGANIC HYDROXYL OR AMINE CONNECTION.

PROCEDURE FOR THE PRODUCTION OF ESTERS OF NICHTREDUZIERENDEM SUGAR OR SUGAR ALCOHOL AND ONE OR MORE FATTY ACIDS.

PROCEDURE FOR THE PRODUCTION OF DEMETHYLEPYPODOPHYLLOTOXIN

PROCEDURE FOR THE PRODUCTION OF N6-SUBSTITUIERTEN AMINOPURIN RIBOFURANOSE NUCLEOSIDEN

Efficient and scalable process for the manufacture of fondaparinux sodium

The present invention relates to a process for the synthesis of the Factor Xa anticoagulent Fondaparinux and related compounds. The invention relates, in addition, to efficient and scalable processes for the synthesis of various intermediates useful in the synthesis of Fondaparinux and related compounds.

Method for the manufacture of 2-fluoro-ara-adenine

A method is described for the manufacture of pure 2-fluoro-ara-adenine of Formula (I) from 2-fluoro-ara-adenine triacetate using potassium carbonate (K 2 CO 3 ), wherein the 2-fluoro-ara-adenine has a reduced dimer contents, as well as the compound 2-fluoro-ara-adenine having a dimer contents of ≦0.3%.

Microprocessing for preparing a polycondensate

The present invention relates to a process for preparing polydextrose by using a microdevice. It further relates to the use of a microdevice for the polycondesation reactions.

NOVEL PROCESS

A single-phase LPS extraction composition comprising water, an alcohol and a further organic solvent, where the amount of water is between about 0.8 to 1.2% (v/v). 1. An LPS extraction composition comprising water , an alcohol and a further organic solvent.2. The composition of wherein the LPS extraction composition is single-phase.3. The composition of or wherein the amount of water in the LPS extraction composition is between about 0.1 and about 1.5% (v/v).4. The composition of any of to wherein the amount of water is about 1% (v/v).5. The composition of any of to wherein the amount of water is about 0.5% (v/v).6. The composition of any of to wherein the alcohol is selected from the list: methanol claim 1 , ethanol claim 1 , isopropanol or butanol.7. The composition of any of to wherein the percentage of alcohol in the LPS extraction composition is between about 5% and about 40% (v/v).8. The composition of wherein the percentage of alcohol is between about 10% (v/v) and about 30% (v/v).9. The composition of any preceding claim wherein the further organic solvent is selected from the group: chloroform claim 7 , alkanes claim 7 , toluene and petroleum ether.10. The composition of wherein the alkane is selected from the group: isooctane claim 9 , ethane claim 9 , heptane and hexane.11. The composition of any preceding claim wherein the percentage of the further organic solvent in the LPS extraction composition is between about 60% (v/v) and about 95% (v/v).12. The composition of wherein the percentage of the further organic solvent is between about 75% (v/v) and about 90% (v/v).13. The composition of any of to wherein the LPS extraction solution comprises chloroform claim 11 , methanol and water.14. The composition of any of to wherein the LPS extraction composition comprises an alkane claim 11 , ethanol and water.15. A composition according to any of to for use in the extraction of LPS from gram negative bacterial cells.16. Use of an LPS extraction composition ...

REBAUDIOSIDE B AND DERIVATIVES

The invention describes compositions that include a sweetener and a salt of a steviol glycoside, wherein the concentration of the components provide an improved taste profile where bitterness, after taste and/or lingering of the sweetener is decreased or eliminated. 2. The purified compound according to claim 1 , wherein M is a sodium or potassium ion.3. The purified compound according to either claim 1 , wherein the sugar is a monosaccharide or an oligosaccharide.4. The purified compound according to claim 3 , wherein the monosaccharide is glucose (dextrose) claim 3 , fructose (levulose) claim 3 , galactose claim 3 , rhamnose claim 3 , xylose and/or ribose.5. The purified compound according to claim 3 , wherein the oligosaccharide is sucrose claim 3 , maltose claim 3 , lactose claim 3 , -glucose-glucose claim 3 , -glucose(-glucose)-glucose claim 3 , -glucose(-rhamnose)-glucose.6. The purified compound according to claim 5 , wherein M is a potassium ion and R is glucose(-glucose-)glucose.7. The purified compound according to claim 5 , wherein M is a sodium ion and R is glucose(-glucose)-glucose.8. A process to prepare a carboxylic acid salt of steviol or a steviol glycoside claim 5 , comprising the step of:reacting steviol or a steviol glycoside with a base, such that a carboxylic acid salt is formed.9. The process of any of claim 8 , wherein the steviol glycoside is raudioside A claim 8 , B claim 8 , D or mixtures thereof.10stevia. A process to prepare a carboxylic acid salt of a extract claim 8 , comprising the step of:{'i': stevia', 'stevia, 'reacting the extract with a base, such that a carboxylic acid salt is formed with one or more constituents of the extract.'}11stevia. The process of claim 10 , wherein the extract constituents comprise one or more of raudioside A claim 10 , B claim 10 , D or mixtures thereof.12. A purified rebaudioside B (RB) sweetener consisting essentially of RB.13. The purified rebaudioside B (RB) sweetener of claim 12 , wherein the ...

RNA SYNTHESIS-PHOSPHORAMIDITES FOR SYNTHETIC RNA IN THE REVERSE DIRECTION, AND APPLICATION IN CONVENIENT INTRODUCTION OF LIGANDS, CHROMOPHORES AND MODIFICATIONS OF SYNTHETIC RNA AT THE 3'-END

The present invention relates to novel phosphoramidites, A-n-bz, C-n-bz, C-n-ac, G-n-ac and U are produced with an HPLC purity of greater than 98% and P NMR purity greater than 99%. A novel process of reverse 5′→3′ directed synthesis of RNA oligomers has been developed and disclosed. Using that method demonstrated high quality RNA synthesis with coupling efficiency approaching 99%. 2. The process according claim 1 , wherein L is cholesterol with the linker or the spacer claim 1 , and n=19.3. The process according to claim 1 , wherein L is polyethyleneglycol (PEG) claim 1 , and n=19.4. An RNA oligonucleotide claim 1 , wherein the RNA oligonucleotide is synthesized by the process according to . This application is a continuation application to U.S. application Ser. No. 12/584,625, filed Sep. 8, 2009, which in turn claims priority to U.S. Provisional Application Ser. No. 61/191,065, filed on Sep. 6, 2008. The entire teachings of the above applications are incorporated herein by reference.This invention relates to the synthesis of novel RNA monomer phosphoramidites, and corresponding solid supports that are suitable for a novel method of RNA oligonucleotide synthesis in reverse 5′→3′ direction. This approach leads to very clean oligonucleotide synthesis allowing for introduction of various modifications at the 3′-end cleanly and efficiently in order to produce high purity and therapeutic grade RNA oligonucleotides.Defined sequence RNA synthesis in the 3′→5′ direction is now well established and currently in use for synthesis and development of a vast variety of therapeutic grade RNA aptamers, tRNAs, siRNA and biologically active RNA molecules. This approach utilizes a ribonucleoside with suitable N-protecting group: generally 5′-Protecting group, the most popular being dimethoxytriphenyl, i.e. the DMT group; 2′-protecting group, out of which most popular is t-Butyldimethylsilyl ether; and, a 3′-phosphoramidite, the most popular of which is cyanoethyl diisopropyl ( ...

Novel Process for the Recovery of Beta Acetylfuranoside

There is provided an improved method for the recovery of residual, unseparated β-ACF from reaction mixtures remaining from an initial synthesis of ACF, which is in particular usable on a large industrial scale, more particularly in the production of capecitabine. 1. A method for recovery of initially not separated β-ACF from mother liquor remaining from the synthesis of ACF , wherein the β-ACF is recovered by a combination of at least one distillation method and at least one chemical reaction step.2. The method according to comprising the following sequential steps:a) Evaporation to less than 1% residual solvent of the mother liquor remaining from an initial synthesis of ACF, to increase the content of residual α/β-ACF from about 8 to 15 weight-% to about 25 to 45 weight-%, followed by distillation to about 60 to 80 weight-% and subsequent crystallization of β-ACF out of the distillate by adding a suitable solvent;b) Chemical conversion of α/β-ACF mixture remaining in the mother liquor of step a), to β-ACF by de-acetylation and subsequent re-acetylation, followed by crystallization of β-ACF by addition of a suitable solvent;c) Optional repetition of step a) and b) in a sequential (clockwise) cyclic process.3. The process according to claim 2 , wherein the distillation to about 60 to 80 weight-% of step a) is carried out at 1 to 3 mbar and 200 to 210° C. heating temperature in a continuous thin-film evaporator.4. The process according to claim 3 , wherein step b) comprises the de-acetylation of α/β-ACF in the presence of a suitable base claim 3 , followed by neutralization with a suitable acid and further followed by the re-acetylation reaction in the presence of suitable base claim 3 , a suitable catalyst and a suitable acetylating agent. This application is a continuation of U.S. application Ser. No. 12/690,167, filed Jan. 20, 2010, now Pending, which claims the benefit of European Patent Application No. 09151384.6, filed Jan. 27, 2009, which is hereby incorporated ...

POST-SYNTHETIC MODIFICATION OF NUCLEIC ACIDS BY INVERSE DIELS-ALDER REACTION

The present invention concerns a method and a kit for the post-synthetic modification of nucleic acids via an inverse Diels-Alder reaction. 1. A method for the post-synthetic modification of nucleic acids , comprising the following steps:(a) preparing norbornene or trans-cyclooctene-modified oligonucleotides(b) preparing modified tetrazines, and(c) reacting the norbornene-modified oligonucleotides with the modified tetrazines via inverse Diels Alder reaction.2. The method of claim 1 , wherein the tetrazines are modified with a compound selected from the group consisting of fluorescent claim 1 , luminescent or phosphorescent dyes claim 1 , and affinity tags.3. The method of claim 1 , wherein the oligonucleotide is singly or multiply modified.4. The method of claim 3 , wherein the oligonucleotide is modified terminally and/or internally.5. The method of claim 4 , wherein the terminal modification is 3′and/or 5′.6. The method of claim 1 , wherein the oligonucleotide has a length between 3 and 500 nucleotides.7. The method of claim 1 , wherein the oligonucleotide is single-stranded or double-stranded DNA or RNA claim 1 , a nucleic acid analog or chimera thereof with DNA and/or RNA or an enyzmatically modified PCR product.9. The method of claim 1 , wherein the tetrazine is labelled with one or more of fluorescent claim 1 , luminescent or phosphorescent dyes claim 1 , or tagged with one or more affinity tags.11. The method of claim 1 , wherein the inverse Diels Alder reaction between the modified oligonucleotide and the modified tetrazin uses equimolar amounts of both components if the oligonucleotide is below 100 nucleotides.12. The method of claim 1 , wherein the inverse Diels Alder reaction between the modified oligonucleotide and the modified tetrazin uses the tetrazine in 2-20-fold excess if the oligonucleotide is larger than 100 nucleotides.13. The method of claim 11 , wherein the inverse Diels Alder reaction takes place between 0 and 100° C. in aqueous media.14. ...

PROCESS FOR PERPARING FONDAPARINUX SODIUM AND INTERMEDIATES USEFUL IN THE SYNTHESIS THEREOF

Processes for the synthesis of the Factor Xa anticoagulent Fondaparinux, and related compounds are described. Also described are protected pentasaccharide intermediates as well as efficient and scalable processes for the industrial scale production of Fondaparinux sodium by conversion of the protected pentasaccharide intermediates via a sequence of deprotection and sulfonation reactions. 114-. (canceled)18. The process of claim 17 , wherein deprotecting step (a) comprises treatment with a reagent selected from hydrazine claim 17 , hydrazine hydrate claim 17 , hydrazine acetate and RNH—NHwhere Ris aryl claim 17 , heteroaryl or alkyl.19. The process of claim 17 , wherein protecting step (b) comprises treatment with dihydropyran or a dihydropyran derivative and an acid selected from camphor sulfonic acid (CSA) claim 17 , hydrochloric acid (HCl) claim 17 , p-toluenesulfonic acid (pTsOH) and Lewis acids.25. The method of claim 24 , further comprising converting the fondaparinux-THP to fondaparinux sodium.27. The process of claim 26 , further comprising converting the resulting product to Fondaparinux sodium.33. The process of claim 32 , wherein the deprotecting step (a) comprises treatment with a reagent selected from hydrazine claim 32 , hydrazine hydrate claim 32 , hydrazine acetate and RNH—NHwhere Ris aryl claim 32 , heteroaryl or alkyl.34. The process of claim 33 , wherein the deprotecting step (a) comprises treatment with hydrazine.35. The process of claim 32 , wherein the protecting step (b) comprises treatment with dihydropyran or a dihydropyran derivative and an acid selected from camphor sulfonic acid (CSA) claim 32 , hydrochloric acid (HCl) claim 32 , p-toluenesulfonic acid (pTsOH) and Lewis acids.36. The process of claim 35 , wherein the protecting step (b) comprises treatment with dihydropyran and an acid selected from hydrochloric acid and p-toluenesulfonic acid.3743-. (canceled)44. A method of preparing an oligosaccharide comprising a β-glucosamine ...

Method of preparing sucralose-6-ester by catalysis and chlorination of phase transfer catalyst

A method of preparing sucralose-6-ester by catalysis and chlorination of phase transfer catalyst comprises the following steps: add phase transfer catalyst into a prepared Vilsmeier reagent and then drip in DMF solution of sucrose-6-ester at 5-10° C. to obtain a feed solution and after that maintain its temperature of the feed solution for 1-1.5 hours; next, increase temperature of the feed solution to 45-55° C. and maintain the temperature for 1-1.5 hours; next, increase the temperature to 75-85° C. and maintain the temperature for 1-1.5 hours; next, increase the temperature to 108-109° C., maintain the temperature for 2.5-3 hours and then remove a chlorine-containing solvent from the feed solution by concentration in reduced pressure for evaporation. After that, cool down the feed solution to room temperature and then pump in ammonia into the feed solution for neutralization.

Multidimensional Supramolecular Structures Essentially Made of Assembled I-Motif Tetramers

The present invention pertains to a supramolecular structure based on i-motif tetramers of C—X—Coligonucleotides, wherein m and n are integers comprised between 2 and 9, and X is a linker such as A, T, G, a modified deoxynucleotide or a diol spacer. These supramolecular structures can be dissociated, when necessary, by a mere pH change. The present invention also relates to methods for obtaining such a supramolecular structure. 1. (canceled)2. A supramolecular structure comprising N C—X—C(SEQ ID No: 1) oligonucleotides , wherein m and n are integers comprised between 2 and 7 , preferably between 3 and 7 , X is selected in the group consisting of A , T , G , a modified deoxynucleotide and a diol spacer , N an integer ≧8 and wherein each oligonucleotide is part of an i-motif tetramer.3. The supramolecular structure of claim 2 , wherein m≠n.4. The supramolecular structure of claim 2 , wherein (m claim 2 , n) is selected in the group of (4 claim 2 , 7) and (7 claim 2 , 4).5. The supramolecular structure according to claim 2 , wherein X=G.6. The supramolecular structure according to claim 2 , which comprises oligonucleotides having different sequences.7. The supramolecular structure according to claim 6 , comprising oligonucleotides of sequence C—X—C(SEQ ID No: 1) and terminator oligonucleotides.8. The supramolecular structure according to claim 7 , wherein at least part of said terminator oligonucleotides are covalently linked to a reactive group.9. The supramolecular structure according to claim 2 , wherein N≧50.10. A process for producing a supramolecular structure according to claim 2 , wherein said process comprises the following steps:{'sub': m', 'n, '(i) incubating a solution of oligonucleotides of sequence C—X—C(SEQ ID No: 1) wherein n and m are integers comprised between 2 and 9, preferably between 3 and 7, and X is selected in the group consisting of A, T, G, a modified deoxynucleotide and a diol spacer, in a buffer having a pH in the range 3 to 6, and'}(ii) ...

METHOD FOR THE SYNTHESIS OF A TRISACCHARIDE

The present invention relates to an improved synthesis of a trisaccharide of the formula (1), novel intermediates used in the synthesis and the preparation of the intermediates. 119-. (canceled)21. The method according to claim 20 , characterized in that the catalytic hydrogenolysis is carried out in water claim 20 , in one or more C-Calcohols claim 20 , in a mixture water and one or more C-Calcohols claim 20 , or in a mixture of water claim 20 , one or more C-Calcohols and acetic acid claim 20 , in the presence of palladium on charcoal or palladium black.22. The method according to claim 20 , characterized in that O-(2 claim 20 ,3 claim 20 ,4-tri-O-benzyl-α-L-fucopyranosyl)-(1→2)-O-β-D-galactopyranosyl-(1→4)-D-glucose of the general formula 1 in hydrated form claim 20 , in crystalline water free form or in a mixture of hydrated and crystalline water free forms is applied.24. The compound according to claim 23 , wherein Rand R claim 23 , independently from each other claim 23 , means benzyl claim 23 , 4-methylbenzyl claim 23 , benzyloxycarbonyl claim 23 , naphthylmethyl claim 23 , 3-phenylbenzyl claim 23 , 4-chlorobenzyl claim 23 , 4-methoxybenzyl claim 23 , 3 claim 23 ,4-dimethoxybenzyl claim 23 , 2 claim 23 ,4 claim 23 ,6-trimethylbenzyl or 2 claim 23 ,3 claim 23 ,4 claim 23 ,5 claim 23 ,6-pentamethylbenzyl claim 23 , benzyl or 4-methylbenzyl and Ris H.27. The method according to claim 26 , characterized in that the acid catalyzed mild hydrolysis is conducted in aqueous acetic acid solution.28. The method according to claim 26 , characterized in that compounds of general formula 2 claim 26 , wherein R and R′ mean methyl claim 26 , one of the Rand Rgroups or both Rand Rgroups are 4-methylbenzyl and Ris H claim 26 , is applied.31. The method according to claim 30 , characterized in that the acid catalyzed mild hydrolysis is carried out in ethyl acetate/acetonitrile/water wherein the proportion of the ethyl acetate is more than 40 v/v %.32. The method according to ...

METAL PARTICLES FOR SURFACE-ENHANCED RAMAN SCATTERING AND MOLECULAR SENSING

There is provided a high-sensitive Raman scattering sensing by regulating in metal nanoparticles for enhanced Raman scattering, particularly the strength of the enhanced electric field by controlling the distance between the particles to impart very strong Raman scattering properties. A metal nanoparticle material for molecular sensing, the metal nanoparticle material comprising: a metal nanoparticle aggregate including three to ten metal nanoparticles connected to each other through an organic molecule so that adjacent metal nanoparticles are bonded and spaced apart a predetermined distance, the aggregate containing a Raman active molecule within a field applied to the aggregate, wherein the metal nanoparticle material emits enhanced Raman scattering light from the Raman active molecule in an enhanced electric field; a method for producing the metal nanoparticle material for molecular sensing; and a molecular sensing by use of the metal nanoparticle material for molecular sensing. 1. A metal nanoparticle material for molecular sensing , the metal nanoparticle material comprising:a metal nanoparticle aggregate including three to ten metal nanoparticles connected to each other through an organic molecule so that adjacent metal nanoparticles are bonded and spaced apart a predetermined distance, the aggregate containing a Raman active molecule within a field applied to the aggregate, whereinthe metal nanoparticle material emits enhanced Raman scattering light from the Raman active molecule in an enhanced electric field.2. The metal nanoparticle material for molecular sensing according to claim 1 , wherein the metal nanoparticles are of a metallic element having a resonance wavelength producing surface plasmon resonance in regions ranging from an ultraviolet region to an infrared region.3. The metal nanoparticle material for molecular sensing according to claim 1 , wherein the metal nanoparticles are particles having an average particle diameter of 1 nm to 100 nm.4. The ...

CRYSTAL FORM OF 4-ISOPROPYLPHENYL GLUCITOL COMPOUND AND PROCESS FOR PRODUCTION THEREOF

A highly stable crystal of (1S)-1,5-anhydro-1-[5-(4-{(1E)-4-[(1-{[2-(dimethylamino)ethyl]amino}-2-methyl-1-oxopropan-2-yl)amino]-3,3-dimethyl-4-oxobut-1-en-1-yl}benzyl)-2-methoxy-4-(propan-2-yl)phenyl]-D-glucitol, and a process for producing the crystal are provided. Specifically, an ethanolate having the following physical properties, and a plurality of other crystal forms transformed from the ethanolate are provided: 1. A crystal of an ethanolate of (1S)-1 ,5-anhydro-1-[5-(4-{(1E)-4-[(1-{[2-(dimethylamino)ethyl]amino}-2-methyl-1-oxopropan-2-yl)amino]-3 ,3-dimethyl-4-oxobut-1-en-1-yl}benzyl)-2-methoxy-4-(propan-2-yl)phenyl]-D-glucitol having physical properties (a) to (c) mentioned below:(a) Having peaks at 2θ=5.9 degrees, 17.1 degrees, 17.6 degrees and 21.5 degrees in X-ray powder diffraction (Cu—Kα);{'sup': −1', '−1', '−1', '−1', '−1', '−1, '(b) Showing characteristic absorption bands at 3538 cm, 3357 cm, 2964 cm, 1673 cm, 1634 cmand 1505 cmin an infrared absorption spectrum; and'}(c) Having a melting point in a vicinity of 111° C.2. A process for producing a crystal having physical properties (a) to (c) mentioned below , comprising:dissolving (1S)-1,5-anhydro-1-[5-(4-{(1E)-4-[(1-{[2-(dimethylamino)ethyl]amino}-2-methyl-1-oxopropan-2-yl)amino]-3,3-dimethyl-4-oxobut-1-en-1-yl}benzyl)-2-methoxy-4-(propan-2-yl)phenyl]-D-glucitol in ethanol or a mixture of ethanol and an organic solvent miscible with ethanol;then effecting crystallization at 0 to 80° C.; anddrying the resulting crystal at 50° C. or lower.(a) Having peaks at 2θ=5.9 degrees, 17.1 degrees, 17.6 degrees and 21.5 degrees in X-ray powder diffraction (Cu—Kα);{'sup': −1', '−1', '−1', '−1', '−1', '−1, '(b) Showing characteristic absorption bands at 3538 cm, 3357 cm, 2964 cm, 1673 cm, 1634 cmand 1505 cmin an infrared absorption spectrum; and'}(c) Having a melting point in a vicinity of 111° C.3. A crystal of (1S)-1 ,5-anhydro-1-[5-(4-{(1E)-4-[(1-{[2-(dimethylamino)ethyl]amino}-2-methyl-1-oxopropan-2-yl)amino]- ...

Alpha-selective glycosylation method

The present invention provides an α-selective glycosylation method. The α-selective glycosylation method includes performing a reaction of a donor having a saccharide structure and a formamide-containing compound to form a glycosyl imidate compound; and in one pot environment, performing an addition reaction of the glycosyl imidate compound and an acceptor having a hydroxyl group to form an α-glycoside with high α-selectivity. The α-selective glycosylation method is applicable to the large scale production and easy to recover the formamide-containing compound.

PROCESS FOR CONJUGATION OF NHS ESTERS WITH OLIGONUCLEOTIDES

The present invention provides processes for the conjugation of NHS esters to amino-modified oligonucleotides. The processes provide the amino-modified oligonucleotide on a solid support such that conjugation can be carried out under conditions that can accommodate a wide variety of NHS esters and oligonucleotides. 1. A process for conjugating a N-hydroxysuccinimide ester with an amino-modified oligonucleotide , the process comprising contacting the N-hydroxysuccinimide ester with the amino-modified oligonucleotide , wherein the amino-modified oligonucleotide is non-covalently bound to an ion exchange support.3. The process of claim 1 , wherein Rcomprises a fluorescent moiety claim 1 , a dye claim 1 , or a label.4. The process of claim 1 , wherein the amino-modified oligonucleotide comprises from about 5 to about 500 bases.5. The process of claim 1 , wherein the amino-modified oligonucleotide has a mass-average molecular weight of about 500 to about 100 claim 1 ,000 Da.6. The process of claim 1 , wherein the amino-modified oligonucleotide has a mass-average molecular weight of about 1 claim 1 ,500 to about 40 claim 1 ,000 Da.7. The process of claim 1 , wherein the amino group comprising the amino-modified oligonucleotide is free during conjugation.8. The process of claim 1 , wherein conjugation is conducted in a non-aqueous environment.9. The process of claim 1 , wherein the ion exchange support comprises a strong base exchanger.10. The process of claim 1 , wherein the ion exchange support comprises a quaternary or tertiary amine.11. A process for conjugating an N-hydroxysuccinimide ester with an amino-modified oligonucleotide claim 1 , the process comprising contacting the N-hydroxysuccinimide ester with the amino-modified oligonucleotide bound to a solid support claim 1 , wherein the process is conducted in a non-aqueous environment.13. The process of claim 11 , wherein Rcomprises a fluorescent moiety claim 11 , a dye claim 11 , or a label.14. The process of claim ...

OLIGONUCLEOTIDE SPECIFIC UPTAKE OF NANOCONJUGATES

The present invention concerns nanoparticles functionalized with an oligonucleotide and a domain for a variety of uses, including but not limited to gene regulation. More specifically, the disclosure provides a nanoparticle that is taken up by a cell at an efficiency different than a nanoparticle functionalized with the same oligonucleotide but does not contain a domain. 1. A nanoparticle functionalized with an oligonucleotide and a domain , the nanoparticle having the property of being taken up by a cell at an efficiency different than a nanoparticle functionalized with the same oligonucleotide but lacking the domain.2. The nanoparticle of wherein the domain is located 5′ to the oligonucleotide.3. The nanoparticle of wherein the domain is located 3′ to the oligonucleotide.4. The nanoparticle of wherein the domain is located at an internal region within the oligonucleotide.5. The nanoparticle of wherein the domain is colinear with the oligonucleotide.6. The nanoparticle of functionalized with a second oligonucleotide and the domain is associated with the second oligonucleotide.7. The nanoparticle of wherein the domain comprises a polythymidine (polyT) sequence comprising more than one thymidine residue.8. The nanoparticle of wherein the domain comprises a polythymidine (polyT) sequence comprising two thymidine residues.9. The nanoparticle of wherein the domain comprises a polythymidine (polyT) sequence comprising two claim 1 , three claim 1 , four claim 1 , five claim 1 , six claim 1 , seven claim 1 , eight claim 1 , nine claim 1 , ten claim 1 , eleven claim 1 , twelve claim 1 , thirteen claim 1 , fourteen claim 1 , fifteen claim 1 , sixteen claim 1 , seventeen claim 1 , eighteen claim 1 , nineteen claim 1 , or twenty thymidine residues.10. The nanoparticle of wherein the domain comprises a phosphate polymer (C3 residue).11. The nanoparticle of wherein the domain comprises two or more phosphate polymers (C3 residues).12. A method of modulating cellular uptake ...

NOVEL SYNTHESIS OF 5-DEOXY-5'-FLUOROCYTIDINE COMPOUNDS

This invention relates to a process of synthesizing a β-nucleoside compound of formula (I): 2. The process of claim 1 , wherein the base is selected from the group consisting of pyridine claim 1 , immidazole claim 1 , ammonium claim 1 , monoalkylamine claim 1 , dialkylamine claim 1 , trialkylamine claim 1 , sodium carbonate claim 1 , and potassium carbonate.3. The process of claim 1 , wherein the solvent is acetone claim 1 , acetonitrile claim 1 , dimethylformamide claim 1 , ethyl acetate claim 1 , 1 claim 1 ,2-dichloroethane (DCE) claim 1 , dimethylacetamide (DMAC) claim 1 , dimethylsulfoxide (DMSO) claim 1 , tetrahydrofuran claim 1 , isopropyl acohol claim 1 , acetonitrile claim 1 , or nitromethane claim 1 , or a mixture of ACN/HO or acetone/HO.4. The process of claim 1 , wherein X is Cl claim 1 , 4-nitrophenoxy claim 1 , or N-succinimidyloxy.5. The process of claim 1 , wherein Ris alkyl.6. The process of claim 5 , wherein Ris n-pentyl.7. The process of claim 1 , wherein the base is pyridine or immidazole.8. The process of claim 6 , wherein X is Cl claim 6 , 4-nitrophenoxy claim 6 , or N-succinimidyloxy.9. The process of claim 8 , wherein the base is pyridine or immidazole.10. The process of claim 9 , wherein the solvent is acetone claim 9 , acetonitrile claim 9 , dimethylformamide claim 9 , ethyl acetate claim 9 , 1 claim 9 ,2-dichloroethane (DCE) claim 9 , dimethylacetamide (DMAC) claim 9 , dimethylsulfoxide (DMSO) claim 9 , tetrahydrofuran claim 9 , isopropyl acohol claim 9 , acetonitrile claim 9 , or nitromethane claim 9 , or a mixture of ACN/HO or acetone/HO.11. The process of claim 10 , wherein the solvent is DMF claim 10 , DMSO claim 10 , or DMAC.12. The process of claim 11 , wherein X is Cl.13. The process of claim 12 , where the base is pyridine.14. The process of claim 13 , wherein the reaction is carried out at a temperature of 50-100° C.15. The process of claim 14 , wherein the reaction is carried out at a temperature of 65-80° C.16. The process of ...

MODIFIED NUCLEOTIDES

The invention provides modified nucleotide or nucleoside molecule comprising a purine or pyrimidine base and a ribose or deoxyribose sugar moiety having a removable 3′-OH blocking group covalently attached thereto, such that the 3′ carbon atom has attached a group of the structure —O—Z wherein Z is any of —C(R′)2-O—R″, —C(R′)2-N(R″)2, —C(R′)2-N(H)R″, —C(R′)2-S—R″ and —C(R′)2-F, wherein each R″ is or is part of a removable protecting group; each R′ is independently a hydrogen atom, an alkyl, substituted alkyl, arylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclic, acyl, cyano, alkoxy, aryloxy, heteroaryloxy or amido group, or a detectable label attached through a linking group; or (R′)2 represents an alkylidene group of formula ═C(R′″)2 wherein each R′″ may be the same or different and is selected from the group comprising hydrogen and halogen atoms and alkyl groups; and wherein said molecule may be reacted to yield an intermediate in which each R″ is exchanged for H or, where Z is —C(R′) 2-F, the F is exchanged for OH, SH or NH2, preferably OH, which intermediate dissociates under aqueous conditions to afford a molecule with a free 3′OH; with the proviso that where Z is —C(R′)2-S—R″, both R′ groups are not H. 118-. (canceled)19. A method of converting a compound of formula R—O-allyl , RN(allyl) , RNH(allyl) , RN(allyl)or R—S-allyl to a corresponding compound in which the allyl group is removed and replaced by hydrogen , said method comprising the steps of reacting a compound of formula R—O-allyl , RN(allyl) , RNH(allyl) , RN(allyl)or R—S-allyl in aqueous solution with a transition metal comprising a transition metal and one or more bands selected from the group comprising water-soluble phosphine and water-soluble nitrogen-containing phosphine ligands , wherein the or each R is a water-soluble biological molecule , which is part of a nucleoside , a nucleotide or polynucleotide molecule , wherein said nucleoside , nucleotide or polynucleotide further comprises a ...

Low Temperature Chlorination of Carbohydrates

Disclosed is a method of chlorinating a carbohydrate or derivative thereof, for example, a sucrose-6-ester at the 4,1′, and 6′ positions, with irreversible removal of HCl formed during the reaction to form the chlorinated carbohydrate or derivative thereof, for example, a 4,1′,6′-trichloro-4,1′,6′-trideoxy-6-O-ester of galactosucrose (TGS-6E). The irreversible removal of HCl can be carried out by an irreversible physical process and/or an irreversible chemical process. Sucralose, an artificial sweetener, can be prepared by deesterification of the TGS-6E. The chlorination reaction takes place at low temperatures and the desired chlorinated product is obtained in high yields and in high purities. 1. A method for chlorinating a carbohydrate or a derivative thereof comprising reacting the carbohydrate or derivative thereof with a chlorinating agent and irreversibly removing during chlorination the hydrogen chloride produced by the reaction of the chlorinating agent with the carbohydrate or derivative thereof.2. The method of claim 1 , wherein the carbohydrate or derivative thereof is a sugar or derivative thereof.3. The method of claim 2 , wherein the sugar derivative is a sugar ester.4. The method of claim 3 , wherein the sugar ester is a sucrose-6-ester.5. The method of claim 4 , wherein the chlorinated product obtained is 4 claim 4 ,1′ claim 4 ,6′-trichloro-4 claim 4 ,1′ claim 4 ,6′-trideoxy-6-O-ester of galactosucrose (TGS-6E).6. The method of claim 1 , wherein the chlorinating agent is an acid chloride.7. The method of claim 6 , wherein the chlorinating agent is a Vilsmeier Reagent having the formula: [XYC═NR]Cl claim 6 , wherein X is hydrogen claim 6 , aryl claim 6 , or alkyl claim 6 , wherein the aryl or alkyl is optionally substituted with a halogen claim 6 , alkoxy claim 6 , thioalkoxy claim 6 , amido claim 6 , or cyano; Y is a leaving group; and R is hydrogen or alkyl which is optionally substituted with halogen claim 6 , alkoxy claim 6 , thioalkoxy claim 6 , ...

2'-O-MODIFIED RNA

[Problem] 2. The ribonucleoside claim 1 , the ribonucleotide claim 1 , or the derivative thereof having a protective group at the 2′-position according to claim 1 ,{'sup': '4', 'wherein R′ to Rmay be identical or different, and each represents a hydrogen atom, a methyl group or an ethyl group,'}{'sup': 5', '6, 'sub': '1-3', 'Rand Rmay be identical or different, and each represents a hydrogen atom, a halogen atom, or a Chaloalkyl group, and'}{'sup': '7', 'Rrepresents a halogen atom.'}3. The ribonucleoside claim 1 , the ribonucleotide claim 1 , or the derivative thereof having a protective group at the 2′-position according to claim 1 ,{'sup': 1', '4, 'wherein all of Rto Rrepresent a hydrogen atom,'}{'sup': 5', '6, 'Rand Rmay be identical or different, and each represents a hydrogen atom, a fluorine atom, a chlorine atom or a bromine atom, and'}{'sup': '7', 'Rrepresents a fluorine atom, a chlorine atom or a bromine atom.'}4. The ribonucleoside claim 1 , the ribonucleotide claim 1 , or the derivative thereof having a protective group at the 2′-position according to claim 1 ,{'sup': 1', '5, 'wherein all of Rto Rrepresent a hydrogen atom,'}{'sup': '6', 'Rrepresents a hydrogen atom, a fluorine atom or a chlorine atom, and'}{'sup': '7', 'Rrepresents a fluorine atom or a chlorine atom.'}5. The ribonucleoside claim 1 , the ribonucleotide claim 1 , or the derivative thereof having a protective group at the 2′-position according to claim 1 ,{'sup': 1', '5, 'wherein all of Rto Rrepresent a hydrogen atom,'}{'sup': '6', 'Rrepresents a hydrogen atom, or a chlorine atom, and'}{'sup': '7', 'Rrepresents a chlorine atom.'}6. The ribonucleoside claim 1 , the ribonucleotide claim 1 , or the derivative thereof having a protective group at the 2′-position according to claim 1 , which is2′-O-(2-chloro)ethoxymethyl-3′,5′-O-(1,1,3,3-tetraisopropyldisiloxane-1,3diyl)nucleic acid base B,2′-O-(2,2-dichloro)ethoxymethyl-3′,5′-O-(1,1,3,3-tetraisopropyldisiloxane-1,3diyl)nucleic acid base B,2′-O-( ...

FUNCTIONALIZED 3-ALKYNYL PYRAZOLOPYRIMIDINE ANALOGUES AS UNIVERSAL BASES AND METHODS OF USE

3-alkynyl inosine analogs and their uses as universal bases are provided. The inosine analogues can be incorporated into nucleic acid primers and probes. They do not significantly destabilize nucleic acid duplexes. As a result, the novel nucleic acid primers and probes incorporating the inosine analogues can be used in a variety of methods. The analogs function unexpectedly well as universal bases. Not only do they stabilize duplexes substantially more than hypoxanthine opposite A, C, T, and G but they are also recognized in primers by polymerases, allowing efficient amplification. 2. The method of claim 1 , wherein the mismatched duplex has substantially the same stability as a corresponding duplex with a natural base in place of 3-alkynyl-1H-pyrazolo[3 claim 1 ,4-d]pyrimidin-4(5H)-one analogue.3. The method of claim 1 , wherein the mismatched base is A claim 1 , T or C.4. The method of wherein the mismatched base is G.5. The method of wherein the 3-alkynyl-1H-pyrazolo[3 claim 1 ,4-d]pyrimidin-4(5H)-one analogue is substituted with pyrene.6. A method for monitoring of polynucleotide amplification of a set of target nucleic acid sequences claim 1 , comprising:(a) providing a mixture comprising a sample containing the target nucleic acid sequences, one or more than one oligonucleotide primers substantially complementary to a portion of the target nucleic acid sequences, a polymerizing enzyme, nucleotide substrates, and a detectable nucleic acid oligomer probe of between 5 and 100 bases,wherein said detectable nucleic acid oligomer probe has a backbone component selected from the group consisting of a sugar phosphate backbone, a modified sugar phosphate backbone, a locked nucleic acid backbone, a peptidic backbone, or a variant thereof,wherein said nucleic acid oligomer probe has a sequence substantially complementary to a probe region of the target nucleic acid sequence,wherein said nucleic acid oligomer probe comprises a fluorophore,wherein at least one of said ...

EFFICIENT AND SCALABLE PROCESS FOR THE MANUFACTURE OF FONDAPARINUX SODIUM

The present invention relates to a process for the synthesis of the Factor Xa anticoagulent Fondaparinux and related compounds. The invention relates, in addition, to efficient and scalable processes for the synthesis of various intermediates useful in the synthesis of Fondaparinux and related compounds. 118-. (canceled)20. The process of claim 19 , further comprising converting the monosaccharide AMod3 to Fondaparinux sodium. This application claims the benefit of U.S. Provisional Patent Application No. 61/256,855, filed Oct. 30, 2009, which is hereby incorporated by reference. This application incorporates by reference U.S. Provisional Application Ser. No. 61/230,557, filed Jul. 31, 2009 and U.S. patent application Ser. No. 12/847,719, filed Jul. 30, 2010.The present invention relates to a process for the synthesis of the Factor Xa anticoagulent Fondaparinux and related compounds. The invention relates, in addition, to efficient and scalable processes for the synthesis of various intermediates useful in the synthesis of Fondaparinux and related compounds.In U.S. Pat. No. 7,468,358, Fondaparinux sodium is described as the “only anticoagulant thought to be completely free of risk from HIT-2 induction.” The biochemical and pharmacologic rationale for the development of a heparin pentasaccharide in 86(1). 1-36, 1997 by Walenga et al. cited the recently approved synthetic pentasaccharide Factor Xa inhibitor Fondaparinux sodium. Fondaparinux has also been described in Walenga et al., , Vol. 11, 397-407, 2002 and Bauer, & , Vol. 17, No. 1, 89-104, 2004.Fondaparinux sodium is a linear octasulfated pentasaccharide (oligosaccharide with five monosaccharide units) molecule having five sulfate esters on oxygen (O-sulfated moieties) and three sulfates on a nitrogen (N-sulfated moieties). In addition, Fondaparinux contains five hydroxyl groups in the molecule that are not sulfated and two sodium carboxylates. Out of five saccharides, there are three glucosamine derivatives and ...

OLIGONUCLEOTIDE WITH PROTECTED BASE

The present invention provides a protected nucleotide for elongation, which can be purified efficiently and in a high yield by a liquid-liquid extraction operation, and can achieve an oligonucleotide production method by a phosphoramidite method. 2. The oligonucleotide comprising a protected base of according to claim 1 , wherein q is 0.4. The oligonucleotide comprising a protected base according to claim 3 , wherein R claim 3 , R claim 3 , Rin the number of l claim 3 , Rand Rare each independently a branched chain alkyl group or branched chain alkenyl group selected from the group consisting of a 2 claim 3 ,6 claim 3 ,10 claim 3 ,14-tetramethylpentadecyl group claim 3 , a 2 claim 3 ,6 claim 3 ,10-trimethylundecyl group claim 3 , a 2 claim 3 ,2 claim 3 ,4 claim 3 ,8 claim 3 ,10 claim 3 ,10-hexamethyl-5-undecyl group claim 3 , a 2 claim 3 ,6 claim 3 ,10-trimethylundeca-1 claim 3 ,5 claim 3 ,9-trienyl group claim 3 , a 2 claim 3 ,6-dimethylheptyl group claim 3 , a 2 claim 3 ,6-dimethylhept-5-enyl group claim 3 , a 2 claim 3 ,6-dimethylhepta-1 claim 3 ,5-dienyl group claim 3 , a 9-nonadecyl group claim 3 , a 12-methyltridecyl group claim 3 , an 11-methyltridecyl group claim 3 , an 11-methyldodecyl group claim 3 , a 10-methylundecyl group claim 3 , an 8-heptadecyl group claim 3 , a 7-pentadecyl group claim 3 , a 7-methyloctyl group claim 3 , a 3-methyloctyl group claim 3 , a 3 claim 3 ,7-dimethyloctyl group claim 3 , a 3-methylheptyl group claim 3 , a 3-ethylheptyl group claim 3 , a 5-undecyl group claim 3 , a 2-heptyl group claim 3 , a 2-methyl-2-hexyl group claim 3 , a 2-hexyl group claim 3 , a 3-heptyl group claim 3 , a 4-heptyl group claim 3 , a 4-methyl-pentyl group claim 3 , a 3-methyl-pentyl group claim 3 , and a 2 claim 3 ,4 claim 3 ,4-trimethylpentyl group; or a straight chain alkyl group selected from the group consisting of a tetradecyl group claim 3 , a tridecyl group claim 3 , a dodecyl group claim 3 , an undecyl group claim 3 , a decyl group claim 3 , a ...

TRISACCHARIDE DERIVATES, AND THEIR USE AS ADJUVANTS

The present invention relates to the use of trisaccharide derivates comprising a substituted trisaccharide core, which trisaccharide core is fully substituted with fatty acid ester groups, and optionally one or more anionic groups as adjuvants, to the trisaccharide derivates as such, to a method for preparing such trisaccharides, to trisaccharides obtained with such method, to adjuvant compositions comprising such trisaccharide derivates and to a vaccine or kit comprising such adjuvant compositions. 138-. (canceled)39. An adjuvant composition comprising:a trisaccharide derivate as the adjuvant, which derivate comprises a substituted trisaccharide core, which trisaccharide core is fully substituted with fatty acid ester groups, and optionally one or more anionic groups; andat least one of a pharmaceutical acceptable excipient and diluent.40. The adjuvant according to claim 39 , wherein the substituted trisaccharide core is derived from raffinose claim 39 , melezitose claim 39 , maltotriose claim 39 , nigerotriose claim 39 , maltotriulose or kestose claim 39 , preferably raffinose claim 39 , melezitose or maltotriose claim 39 , most preferably raffinose or maltotriose.41. The adjuvant according to claim 39 , wherein the substituted trisaccharide core comprises one or two sulphate ester or phosphate ester groups as anionic groups.42. The adjuvant according to claim 41 , wherein the anionic group is a sulphate ester.43. The adjuvant according to claim 39 , wherein the fatty acid ester group is an ester of a straight claim 39 , branched claim 39 , saturated or unsaturated fatty acid with a chain length of 4 to 20 carbon atoms.44. The adjuvant according to claim 39 , wherein the fatty acid ester is the ester of lauric acid claim 39 , myristic acid claim 39 , palmitic acid claim 39 , stearic acid or arachidic acid.45. The adjuvant according to claim 39 , wherein the fatty acid ester groups of the substituted trisaccharide core are all identical.46. The adjuvant according ...

METHODS FOR THE PREPARATION OF DIASTEROMERICALLY PURE PHOSPHORAMIDATE PRODRUGS

Provided are methods and intermediates for preparing diastereomerically pure phosphoramidate prodrugs of nucleosides of Formulas Ia and Ib: 8. The method of wherein Ris H claim 1 , halogen claim 1 , optionally substituted (C-C)alkyl claim 1 , optionally substituted (C-C)alkenyl or optionally substituted (C-C)alkynyl.9. The method of wherein Ris H claim 8 , CHor F.10. The method of wherein each R claim 1 , Rand Ris H.11. The method of wherein one of Ror Ris H and the other of Ror Ris optionally substituted (C-C)alkyl.12. The method of wherein Ris optionally substituted (C-C)alkyl.13. The method of wherein Ris NRRor OR.14. The method of wherein Ris H or NRR.15. The method of wherein when Ror Ris ORor NRRthen each Rand Rof said ORor NRRis H.16. The method of wherein Ris NHand Ris H.17. The method of wherein Ris optionally substituted (C-C)aryl.19. The method of wherein the compound of Formula VIII is dissolved in an ether solvent and the crystallization is induced by addition of a C-Chydrocarbon.20. The method of wherein the compound of Formula VIII is dissolved in diethyl ether or methyl-t-butyl ether and crystallization is induced by the addition of hexane.21. The method of wherein the compound of Formula VIII is dissolved in diethyl ether and crystallization is induced by the addition of hexane.24. The method of wherein the compound of Formula VIII is dissolved in an ether solvent and the crystallization is induced by addition of a C-Chydrocarbon.25. The method of wherein the compound of Formula VIII is dissolved in diethyl ether or methyl-t-butyl ether and crystallization is induced by the addition of hexane.26. The method of wherein the compound of Formula VIII is dissolved in diethyl ether and crystallization is induced by the addition of hexane.29. The method of wherein Ris H and one of Ror Ris H.30. The method of wherein Ris optionally substituted (C-C)alkyl and Ris optionally substituted (C-C)aryl.31. The method of wherein Ris optionally substituted phenyl.32. ...

Spiroannulated Nucleosides and Process for the Preparation Thereof

We claim a simple strategy for the synthesis of a collection of C(3′)-spirodihydroisobenzo- furannulated and C(3′)-spirodihydroisobenzo-furannulated nucleosides featuring a [2+2+2]-cyclotrimerization as the key reaction. The cyclotrimerization reactions are facile with the unprotected nucleosides having a diyne unit. When both alkynes of the diyne are terminal, the regioselectivity is poor. However, when one of the terminal alkynes is additionally substituted, the cyclotrimerizations are highly diaste reoselective. Since the key bicycloannulation is the final step, this strategy provides flexibility in terms of the alkynes and is thus amenable for the synthesis of a focussed small molecule library. 3. The Spiro annulated nucleoside of general formula I as claimed in is represented by the group of the following compounds{'smallcaps': 'D', '1-[3-C,3-O-(o-Phenylenemethylene)-β--ribofuranosyl]uracil (18){'smallcaps': 'D', '1-[3-C,3-O-(o-Phenylenemethylene)-β--ribofuranosyl]thymine (19){'smallcaps': 'D', '1-[3-C3-O-(o-Phenylenemethylene)-β--ribofuranosyl]5-flurouracil (20){'smallcaps': 'D', '1-[3-C,3-O-{o-(3,4-Di-acetyloxymethyl)-phenylenemethylene}-β--ribofuranosyl]uracil (24){'smallcaps': 'D', '1-[3-C,3-O-{o-{3,4-Di-acetyloxymethyl)-phenylenemethylene}-β--ribofuranosyl]thymine (25){'smallcaps': 'D', '1-[3-C,3-O-{o-(3,4-Di-acetyloxymethyl)-phenylenemethylene}-β--ribofuranosyl]5-flurouracil (26){'smallcaps': 'D', '1- [3-C,3-O-{o-(3,4-Di-acetyloxymethyl)-phenylenemethylene}-β--ribopyranosyl]uracil (27){'smallcaps': 'D', '1-[3-C,3-O-{o-(3,4-Di-acetyloxymethyl)-phenylenemethylene}-β--ribopyranosyl]thymine (28){'smallcaps': 'D', '1- [3-C,3-O-{o-(3,4-Di-acetyloxymethyl)-phenylenemethylene}-β--ribopyranosyl]5-flurouracil (29){'sup': 'n', 'smallcaps': 'D', '1-[3-C,3-O-{o-(¾-Pentyl)-phenylenemethylene}-β--ribofuranosyl]uracil (30){'sup': 'n', 'smallcaps': 'D', '1- [3-C,3-O-{o-(¾-Pentyl)-phenylenemethylene}-β--ribofuranosyl]thymine (31){'sup': 'n', 'smallcaps': 'D', '1-[3-C,3-O-{ ...

MIXED SUPER CRITICAL FLUID HYDROLYSIS AND ALCOHOLYSIS OF CELLULOSE TO FORM GLUCOSE AND GLUCOSE DERIVATIVES

The present invention relates to a process for generating glucose and glucose derivatives from the direct contacting of cellulose, hemicelluloses and/or polysaccharides with a mixed super critical fluid system of alcohol and water whereby the partial pressure of the system provides for both alcoholysis and hydrolysis of the material to generate primarily glucose, and glucose derivatives. 1. A method for making a hexose , a pentose , an alkyl glucoside , or an alkyl pentoside , the method comprising:(a) (i) combining a feedstock with an alcohol and water,wherein the feedstock comprises a cellulosic material, a protein, or both a cellulosic material and a protein; or(ii) combining a feedstock with an alcohol and water,wherein the feedstock comprises a cellulosic material, a hemicellulose-comprising material, or both a cellulosic material and a hemicellulose-comprising material; and(b) reacting the feedstock and the alcohol and water at a temperature in the range of between about 140° C. to 350° C., and at a pressure in a range of between about 500 psig to 3200 psig to cleave the cellulosic material to generate a product comprising a hexose, a pentose, an alkyl glucoside, or an alkyl pentoside.2. The method of claim 1 , wherein the feedstock comprises at least about 10 wt % cellulosic material based on the dry weight of the feedstock.3. The method of claim 1 , wherein the feedstock comprises at least about 10 wt % proteins based on the dry weight of the feedstock.4. The method of claim 1 , wherein the water content of the combination of (a)(ii) before the reaction of (b) is from about 30 wt % to about 300 wt % of the dry weight of the feedstock.5. The method according to claim 1 , wherein said feedstock comprises a rice husk claim 1 , a rice bran claim 1 , a corn stover claim 1 , a corn cob claim 1 , a sugar cane bagasse claim 1 , a palm fiber claim 1 , a palm kernel cake claim 1 , a wood pulp claim 1 , a pine tree material claim 1 , a fir tree material claim 1 , a ...

CATALYTIC GLYCOSYLATION WITH DESIGNER THIOGLYCOSIDE AND NOVEL PROTECTING GROUPS FOR SAME AND FOR SYNTHESIS OF OLIGOSACCHARIDES

A catalytic glycosylation method comprising: installing thioether to an anomeric carbon of a carbohydrate; and catalytically activating the thioether with a non-oxophilic Lewis acid. The thioether may comprise an anomerically stable thioether leaving group. The catalytic glycosylation method may further comprise: utilizing an acid-sensitive ester protecting group as permanent protecting group or using a reactivity-based one-pot glycosylation that employs a single-component catalyst to accelerate an oligosaccharide assembly process. A protecting group to mask hydroxyl functionalities in the production of oligosaccharides, natural products or any molecule having a hydroxyl group comprising an acid-labile ester protecting group. 1. A catalytic glycosylation method comprising:installing thioether to an anomeric carbon of a carbohydrate; andcatalytically activating the thioether with a non-oxophilic Lewis acid.2. The catalytic glycosylation method of wherein the thioether comprises an anomerically stable thioether leaving group.3. The catalytic glycosylation method of further comprising: utilizing an acid-sensitive ester protecting group as permanent protecting group.4. The catalytic glycosylation method of further comprising: using a reactivity-based one-pot glycosylation that employs a single-component catalyst to accelerate an oligosaccharide assembly process.5. The catalytic glycosylation method of further comprising: utilizing an application of a 100%-PEG-based polymer as insoluble support for solid-phase oligosaccharide synthesis.6. The catalytic glycosylation method of further comprising: utilizing a designer thioglycoside that retains basic properties of a parental thioglycoside claim 1 , including the ease of preparation and toleration of backbone protecting group manipulation.7. The catalytic glycosylation method of further comprising: applying an activator permitting an application of highly acid-sensitive protecting groups;applying a 100%-PEG-based polymer as ...

Synthetic Lipid A Derivative

The invention provides functionalized monosaccharides and disaccharides suitable for use in synthesizing a lipid A derivative, as well as methods for synthesizing and using a synthetic lipid A derivative. 2. The compound of wherein Ris tert-butyldimethylsilyl (TBS) or dimethylthexylsilyl (TDS).3. The compound of wherein Ris azido.4. The compound of wherein Ris an amino protecting group comprising 9-fluorenylmethoxycarbamate (Fmoc).5. The compound of wherein Ris a hydroxyl protecting group comprising allyloxycarbonate (Alloc).6. The compound of wherein Ris an amino protecting group comprising 9-fluorenylmethoxycarbamate (Fmoc).7. The compound of wherein Ris a hydroxyl protecting group comprising allyloxycarbonate (Alloc) or levulinate (Lev).8. The compound of wherein Rand Rtogether form a ring comprising an acetal.10. The method of wherein selectively acylating the functionalized disaccharide comprises selectively acylating the functionalized disaccharide at two claim 9 , three or four of positions C-2 claim 9 , C-3 claim 9 , C-2′ and C-3′ of the functionalized disaccharide.11. The method of further comprising phosphorylating the functionalized disaccharide at either or both of the C-1 or C-4′ positions of the functionalized disaccharide.12. The method of further comprising contacting the functionalized disaccharide with a 3-deoxy-D-manno-oct-2-ulosonic acid (KDO) donor to yield a KDO glycoside at the C-6′ position of the functionalized disaccharide.13. The method of wherein Ris tert-butyldimethylsilyl (TBS) or dimethylthexylsilyl (TDS).14. The method of wherein Ris azido.15. The method of wherein Ris an amino protecting group comprising 9-fluorenylmethoxycarbamate (Fmoc).16. The method of wherein Ris a hydroxyl protecting group comprising allyloxycarbonate (Alloc). This application is a continuation application of U.S. application Ser. No. 12/676,253, filed Apr. 19, 2010, which is national stage application of International Application No. PCT/US2008/010394, filed ...

COMPOUNDS

The present invention provides a compound which is a nystatin derivative having an additional double bond present between C28 and C29 and which is further modified relative to nystatin at one or more of positions C5, C7, C9, C10, C11, C16 or at the amino group of mycosamine. 132.-. (canceled)34. A compound as claimed in which is modified at position C5 relative to nystatin.35. A compound as claimed in which is modified at C9 relative to nystatin.36. A compound as claimed in which is modified at C10 relative to nystatin.37. A compound as claimed in which is modified at the amino group of mycosamine.38. A compound as claimed in wherein Rrepresents a hydrogen atom claim 33 , a hydroxyl group or an alkoxy group (e.g. a group —OC) and Ris a hydrogen atom or wherein Rand Rtogether form a carbonyl group.39. A compound as claimed in claims 33 , wherein Rrepresents a hydrogen atom claims 33 , a hydroxyl group or an alkoxy group (e.g. a group —OC) and Ris a hydrogen atom or wherein Rand Rtogether form a carbonyl group.40. A compound as claimed in claim 33 , wherein Rrepresents a hydrogen atom claim 33 , a hydroxyl group or an alkoxy group (e.g. a group —OC) and Ris a hydrogen atom41. A compound as claimed in claim 33 , wherein Rrepresents a hydrogen atom claim 33 , an alkylamino group claim 33 , a sugar or an acyl group and Ris identical to Ror is a hydrogen atom claim 33 , e.g. Ris a hydrogen atom.43. A compound as claimed in wherein Ris methyl claim 42 , CONH(CH)N(CH)or CONH(CH)OH where n is 2 or 3.44. A compound as claimed in claim 33 , wherein Ris an alkylamino group of the formula —(CH)NHor —(CH)N(Calkyl)wherein x is 2 to 6 or is a monosaccharide selected from glucose claim 33 , galactose claim 33 , glucopyranose claim 33 , mannopyranose claim 33 , galactopyranose claim 33 , fructopyranose and tagotopyranose or is an oligosaccharide selected from lactose claim 33 , melibiose claim 33 , sucrose claim 33 , maltose and cellobiose.45. A compound as claimed in claim 33 , ...

Synthesis of deuterated ribo nucleosides, N-protected phosphoramidites, and oligonucleotides

The present invention is directed towards the synthesis of high purity deuterated sugars, deuterated phosphoramidites, deuterated nucleobases, deuterated nucleosides, deuterated oligonucleotides, and deuterated RNA's of defined sequences which can exhibit biochemically useful and biologically valuable properties, thus having potential for therapeutic uses. 2. The modified ribo-oligonucleotide according to wherein W is oxygen and Y is oxygen.3. The modified ribo-oligonucleotide according to wherein W is sulfur and Y is oxygen.4. The modified ribo-oligonucleotide according to wherein at least one deuterium is replaced by a hydrogen.5. The modified ribo-oligonucleotide according to wherein said B is a naturally occurring nucleobase claim 1 , a modified nucleobase claim 1 , or combinations thereof.6. The modified ribo-oligonucleotide according to wherein B includes a purine claim 1 , a pyrimidine claim 1 , or combinations thereof.7. The modified ribo-oligonucleotide according to wherein B is partially or fully deuterated.8. The modified oligonucleotide according to wherein B is deuterioadenine claim 7 , deuteriocytidine claim 7 , deuterioguanine claim 7 , deuteriouracil claim 7 , or combinations thereof.9. The modified ribo-oligonucleotide according to wherein said nucleotide has a variant internucleotide linkage.10. The modified ribo-oligonucleotide according to wherein said ribose sugars are fully deuterated.11. The modified ribo-oligonucleotide according to wherein said ribose sugars are partially deuterated.12. The modified ribo-oligonucleotide according to having a mixture of fully deuterated ribose sugars and partially deuterated ribose sugars.13. The modified ribo-oligonucleotide according to wherein said B′ claim 9 , B″ claim 9 , and B′″ is a naturally occurring nucleobase claim 9 , a modified nucleobase claim 9 , or combinations thereof.14. The modified ribo-oligonucleotide according to wherein B′ claim 12 , B″ claim 12 , and B′″ claim 12 , includes a purine ...

Synthesis of deuterated ribo nucleosides N-protected phosphoramidites, and oligonucleotides

The present invention is directed towards the synthesis of high purity deuterated sugars, deuterated phosphoramidites, deuterated nucleobases, deuterated nucleosides, deuterated oligonucleotides, and deuterated RNA's of defined sequences which can exhibit biochemically useful and biologically valuable properties, thus having potential for therapeutic uses. 2. The modified phosphoramidite according to wherein said R1 is dimethoxytrityl protecting group claim 1 , R2 is t-butyldimethylsilyl protecting group claim 1 , R3 is diiopropylamino protecting group claim 1 , and R4 is a 3′-O-cyanoethyl protecting group.3. The modified phosphoramidite according to wherein said B contains a blocking group.4. The modified phosphoramidite according to wherein said nucleobase is a natural base.5. The modified phosphoramidite according to wherein said natural base is adenine.6. The modified phosphoramidite according to wherein said natural base is guanine.7. The modified phosphoramidite according to wherein said natural base is cytosine.8. The modified phosphoramidite according to wherein said natural base is uracil.9. The modified phosphoramidite according to wherein said nucleobase is a modified nucleobase.10. The modified phosphoramidite according to wherein said modified base is deuteratedadenine.11. The modified phosphoramidite according to wherein said modified base is deuteratedguanine12. The modified phosphoramidite according to wherein said modified base is deuteratedcytosine.13. The modified phosphoramidite according to wherein said modified base is deuterateduracil.14. The modified oligonucleotide according to wherein the ribose sugar is partially deuterated.16. The deuterated oligonucleotide solid support according to wherein said R1 is dimethoxytrityl protecting group claim 15 , R2 is t-butyldimethylsilyl protecting group claim 15 , R4 is succinyl Icaa claim 15 , and R4 is CPG.17. The deuterated oligonucleotide solid support according to wherein said nucleobase is a ...

PHOSPHONATE NUCLEOSIDES USEFUL AS ACTIVE INGREDIENTS IN PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF VIRAL INFECTIONS, AND INTERMEDIATES FOR THEIR PRODUCTION

The invention is directed to processes of preparing phosphonate nucleosides comprising a phosphonalkoxy-substituted five-membered, saturated or unsaturated, oxygen-containing ring coupled to a heterocyclic nucleobase such as a pyrimidine or purine base. These compounds can be described by general formula (II) 2. The process of claim 1 , wherein Ris an O-benzoyl group.3. The process of claim 1 , wherein the Lewis acid catalyst is SnCl.4. The process of claim 1 , further comprising a step of N-protecting the nucleobase with an acyl group prior to the coupling step.5. The process of claim 4 , wherein the acyl group is a benzoyl group or an acetyl group.6. The process of claim 1 , wherein the coupling step is carried out from 0° C. to room temperature.7. The process of claim 1 , further comprising a step of silylating the nucleobase prior to the coupling step.8. The process of claim 7 , wherein silylating is performed with hexamethyldisilane.9. The process of claim 8 , wherein silylating is performed in the presence of ammonium sulphate.10. The process of claim 1 , wherein Ris ORand Ris hydrogen claim 1 , further comprising a step of selectively protecting Rprior to the coupling step.11. The process of claim 1 , wherein Rand Rare each isopropyl.12. The process of claim 1 , wherein Ris benzyl.13. The process of claim 1 , wherein n is 1.14. The process of claim 11 , wherein Ris benzyl.15. The process of claim 11 , wherein n is 1.16. The process of claim 12 , wherein n is 1.17. The process of claim 4 , further comprising a step of deprotecting the nucleobase after the coupling step claim 4 , said deprotecting step being performed under basic conditions.18. The process of claim 17 , wherein said deprotecting step is performed with saturated ammonia in methanol.19. The process of claim 1 , wherein Rand Rare each hydrogen claim 1 , further comprising a final hydrolysis step.20. The process of claim 19 , wherein said final hydrolysis step is performed by treatment with a ...

Processes for the preparation of regadenoson and a new crystalline form thereof

This disclosure relates to an improved process for the preparation of regadenoson, pharmaceutically acceptable salts thereof, and hydrates thereof, and for the preparation of intermediates useful in the synthesis of regadenoson. The disclosure also relates to a new crystalline form of regadenoson. Processes for the preparation of the crystalline form, compositions containing the crystalline form, and methods of use thereof are also described.

2'-O-AMINOOXYMETHYL NUCLEOSIDE DERIVATIVES FOR USE IN THE SYNTHESIS AND MODIFICATION OF NUCLEOSIDES, NUCLEOTIDES AND OLIGONUCLEOTIDES

Disclosed are O-protected compounds of the formula (I): wherein B is an optionally protected nucleobase, and R-Rare as described herein, a method of preparing such compounds, and a method of preparing oligonucleotides such as RNA starting from such compounds. The O-protected compounds have one or more advantages, for example, the 2′-O-protected compound is stable during the various reaction steps involved in oligonucleotide synthesis; the protecting group can be easily removed after the synthesis of the oligonucleotide, for example, by reaction with tetrabutylammonium fluoride; and/or the O-protected groups do not generate DNA/RNA alkylating side products, which have been reported during removal of 2′-O-(2-cyanoethyl)oxymethyl or 2′-O-[2-(4-tolylsulfonyl)ethoxymethyl groups under similar conditions. 2. The compound of claim 1 , wherein the optionally protected nucleobase or the nucleobase is selected from the group consisting of cytosine claim 1 , adenine claim 1 , guanine claim 1 , uracil claim 1 , thymine claim 1 , xanthine claim 1 , hypoxanthine claim 1 , alkyl derivatives thereof claim 1 , amino derivatives thereof claim 1 , halo derivatives thereof claim 1 , 2- or 8-amino adenine claim 1 , 2- or 8-alkyl adenine claim 1 , 5-halo uracil claim 1 , 5-halo cytosine claim 1 , 2 claim 1 ,6-diaminopurine claim 1 , 6-aza uracil claim 1 , 4-thio uracil claim 1 , 5-trifluoromethyl uracil claim 1 , 5-trifluoromethyl cytosine claim 1 , 6-aza thymine claim 1 , 6-thioguanine claim 1 , 7-deazaadenine claim 1 , 7-deazaguanine claim 1 , 8-mercapto adenine claim 1 , 8-thioalkyl adenine claim 1 , 8-hydroxyl/oxo adenine claim 1 , 8-mercapto guanine claim 1 , 8-thioalkyl guanine claim 1 , and 8-hydroxyl/oxo guanine claim 1 , 1-methyladenine claim 1 , 2-methyladenine claim 1 , N-methyladenine claim 1 , N-isopentyladenine claim 1 , 2-methylthio-N-isopentyladenine claim 1 , N claim 1 ,N-dimethyladenine claim 1 , 8-bromoadenine claim 1 , 2-thiocytosine claim 1 , 3-methylcytosine claim 1 ...

REBAUDIOSIDE B AND DERIVATIVES

The invention describes compositions that include a stevia sweetener and a salt of a steviol glycoside, wherein the concentration of the components provide an improved taste profile where bitterness, after taste and/or lingering of the stevia sweetener is decreased or eliminated. 166-. (canceled)67. A stevia composition comprising a mixture consisting essentially of stevia extract , wherein the mixture contains 1% to 30% of purified rebaudioside B by weight , wherein the purity of the rebaudioside B is at least 95% pure , wherein the stevia extract has above 90% purity of total steviol glycoside and the total steviol glycosides contain rebaudioside A and rebaudioside D , wherein the ratio of rebaudioside D to rebaudioside A is from 30:70 to 5:95 by wright , and wherein the ratio of rebaudioside A to rebaudioside B is from 75:25 to 95:5 by weight.68. The stevia composition of claim 67 , wherein the ratio of rebaudioside A to rebaudioside B is from 80:20 to 95:5 by weight.69. The stevia composition of claim 67 , wherein the ratio of rebaudioside A to rebaudioside B is from 85:15 to 95:5 by weight.70. The stevia composition of claim 67 , wherein the ratio of rebaudioside A to rebaudioside B is 90:10 by weight.71. The stevia composition of claim 67 , wherein the rebaudioside B comprises a salt of rebaudioside B.72. The stevia composition of claim 67 , wherein the rebaudioside B comprises an amino acid salt of rebaudioside B.73. The stevia composition of claim 67 , wherein rebaudioside C is absent from the stevia composition.74. The stevia composition of claim 73 , wherein one or more components selected from the group consisting of rebaudioside E claim 73 , F claim 73 , stevioside claim 73 , steviolmonoside claim 73 , steviolbioside claim 73 , rubusoside claim 73 , and dulcoside are absent from the stevia composition.75. A stevia composition comprising rebaudioside A claim 73 , rebaudioside B and rebaudioside D claim 73 , wherein the ratio of rebaudioside A to ...

SCUTELLARIN AMIDE DERIVATIVES, AND PREPARATION METHODS AND USES THEREOF

The present disclosure discloses scutellarin amide derivatives and preparation methods and uses thereof, which belongs to the field of natural drugs and medicinal chemistry. The scutellarin amide derivatives according to the present disclosure and pharmaceutically acceptable salts thereof have a structure as shown in the following general formula I: 2. The compound according to claim 1 , wherein R is a substituted or unsubstituted C-Calkyl group claim 1 , a substituted or unsubstituted benzyl group on the benzene ring claim 1 , and the substituent is a C-Calkyl group claim 1 , a C-Calkoxy group; Ris a substituted or unsubstituted C-Calkyl group claim 1 , a substituted or unsubstituted phenyl group claim 1 , and the substituent is halogen claim 1 , a C-Calkyl group or a C-Calkoxy group.3. The compound according to claim 1 , wherein R is methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , isopropyl claim 1 , n-butyl claim 1 , isobutyl or benzyl; Ris ethyl claim 1 , n-propyl claim 1 , isopropyl claim 1 , n-butyl claim 1 , n-pentyl claim 1 , n-hexyl claim 1 , cyclohexyl claim 1 , phenyl claim 1 , 4-chlorophenyl claim 1 , 3-chlorophenyl claim 1 , 2-chlorophenyl claim 1 , 4-methylphenyl claim 1 , 3-methylphenyl claim 1 , 2-methylphenyl claim 1 , 4-hydroxyphenyl claim 1 , 3-hydroxyphenyl claim 1 , 2-hydroxyphenyl claim 1 , 4-methoxyphenyl claim 1 , 3-methoxyphenyl claim 1 , 2-methoxyphenyl.5. A pharmaceutical composition comprising the compound according to and a pharmaceutically acceptable salt thereof.6. The pharmaceutical composition according to claim 5 , wherein R is a substituted or unsubstituted C-Calkyl group claim 5 , a substituted or unsubstituted benzyl group on the benzene ring claim 5 , and the substituent is a C-Calkyl group claim 5 , a C-Calkoxy group; Ris a substituted or unsubstituted C-Calkyl group claim 5 , a substituted or unsubstituted phenyl group claim 5 , and the substituent is halogen claim 5 , a C-Calkyl group or a C-Calkoxy group.7. The ...

METHODS FOR STUDYING NUCLEOTIDE ACCESSIBILITY IN DNA AND RNA BASED ON LOW-YIELD BISULFITE CONVERSION AND NEXT-GENERATION SEQUENCING

Provided are methods for characterizing nucleotide accessibility and nucleic acid structure at single nucleotide resolution, using a combination of low-yield bisulfite conversion and next-generation sequencing (NGS). Cytosine (C) nucleotides that are in base-paired states or bound to proteins, etc. are less accessible to chemical reactions and thus exhibit lower bisulfite conversion yields. Analysis of NGS results of a low-yield bisulfite conversion product can thus inform nucleotide accessibility and nucleic acid structure. Compared to other methods for chemical probing of nucleic acid structure, the present methods provide higher information throughput, because each NGS read simultaneously reports on the base pair status of multiple nucleotides. 1. A method for low-yield conversion of unmethylated cytosine nucleotides to uracil (U) nucleotides in a target nucleic acid molecule , the method comprising:(a) introducing a bisulfite solution to a sample comprising the target nucleic acid molecule to achieve a final bisulfite concentration of between 0.1 M and 10 M;(b) allowing the bisulfite conversion to react a temperature between 4° C. and 70° C.;(c) stopping the bisulfite conversion reaction through removal of the excess bisulfite; and(d) performing desulfonation.2. The method of claim 1 , wherein unmethylated cytosines that do not participate in base pairing have a C to U conversion rate of no more than 90%.3. The method of claim 1 , wherein the bisulfite concentration is between 4 M and 10 M claim 1 , and the reaction proceeds at a temperature between 4° C. and 55° C. for between 1 minute and 60 minutes.4. The method of claim 1 , wherein the bisulfite concentration is between 4 M and 10 M claim 1 , and the reaction proceeds at a temperature between 45° C. and 70° C. for between 10 seconds and 20 minutes.5. The method of claim 1 , wherein the bisulfite concentration is between 0.5 M and 5 M claim 1 , and the reaction proceeds at a temperature between 45° C. and 70° ...

SYNTHETIC CATALYSTS FOR CARBOHYDRATE PROCESSING

The disclosure relates to molecularly-imprinted cross-linked micelles that can selectively hydrolyze carbohydrates. 1. A molecularly-imprinted cross-linked micelle selective for a glycan , the micelle comprising:an imprint of the functional or structural analogue of a glycan;a binding unit and an acid unit, wherein the binding unit is bindable to the glycan;and the acid unit is proximal to a glycosidic bond of the glycan during binding of the glycan to the binding unit.2. The micelle of claim 1 , wherein the micelle is obtained from the functional or structural analogue of a glycan as a template.3. The micelle of claim 1 , wherein the functional or structural analogue of the glycan is a monosaccharide.4. The micelle of claim 1 , wherein the functional or structural analogue of the glycan is an oligosaccharide or polysaccharide.5. The micelle of claim 1 , wherein the functional or structural analogue of the glycan is glucose claim 1 , maltose claim 1 , or maltotriose.6. The micelle of claim 1 , wherein the acid unit is a double acid.7. The micelle of claim 1 , wherein the acid unit is a Brønsted acid.8. The micelle of claim 7 , wherein the acidic unit is a carboxylic acid claim 7 , sulfonic acid claim 7 , or a phosphonic acid.9. The micelle of claim 1 , wherein the acid unit is a Lewis acid.10. The micelle of claim 1 , wherein the micelle is obtained from cross-linkable surfactants containing one or more functional groups that are polymerizable and cross-linkable.11. The micelle of claim 1 , wherein the micelle comprises surfactants comprising one or more polymerizable vinyl groups that are polymerizable by free radical polymerization.12. The micelle of claim 1 , wherein the micelle comprises a surface and a core and is cross-linked on the surface by covalent bonds.13. The micelle of claim 1 , wherein the micelle is cross-linked in the core by covalent bonds.14. The micelle of claim 1 , wherein the binding unit comprises a boroxole claim 1 , a boronic acid claim 1 , ...

DIAMINOPHENOTHIAZINIUM DERIVATIVES FOR LABELLING BIOMOLECULES, METHOD AND SUBSTRATE FOR LABELLING OLIGONUCLEOTIDES, AND OLIGONUCLEOTIDES OBTAINED

The present invention relates to diaminophenothiazinium derivatives of formula (I); in which R, R, R, R, R, Rand X are as defined in Claim and also the methods for labelling oligonucleotides using such a derivative, labeling substrates and the oligonucleotides which can be obtained by means of such methods or from such labelling substrates. 2. The diaminophenothiazinium derivatives as claimed in claim 1 , characterized in that Aand Aare linear or branched alkylene chains in which from 2 to 6 consecutive carbon atoms separate the oxygen and nitrogen atoms.3. The diaminophenothiazinium derivatives as claimed in claim 1 , characterized in that at least one of the R claim 1 , R claim 1 , Rand Rgroups does not represent an -A-ORgroup as defined in and said R claim 1 , R claim 1 , Ror Rgroup(s) different than -A-ORand that -A-ORrepresent(s) an alkyl group having from 2 to 12 carbon atoms claim 1 , preferably from 4 to 12 carbon atoms.4. The diaminophenothiazinium derivatives as claimed in claim 1 , characterized in that R═R═H.5. The diaminophenothiazinium derivatives as claimed in claim 1 , characterized in that Rrepresents a —P{N[(C-C)alkyl]}(OCHCHC≡N) group claim 1 , such as the —P[N(Pr)](OCHCHC≡N) group.9. A method for labeling an oligonucleotide with a diaminophenothiazinium derivative as claimed in claim 1 , which comprises the growth of an oligonucleotide grafted onto a solid substrate claim 1 , and the replacement of one or more of the nucleotides of which it is formed with one or more of said diaminophenothiazinium derivatives claim 1 , before the oligonucleotide is detached from the solid substrate.10. The labeling method as claimed in claim 9 , characterized in that at least one replacement with a diaminophenothiazinium derivative is carried out before the end of the growth of the oligonucleotide.11. The labeling method as claimed in claim 9 , characterized in that at least one substitution with a diaminophenothiazinium derivative is carried out in the 3′ or 5′ ...

PROCESS FOR THE PREPARATION OF DIOSMIN

The present invention relates to a process for the preparation of diosmin from hesperidin. The process involves the oxidation of acylated hesperidin with iodine or bromine in a C-Ccarboxylic acid medium and subsequent treatment with an inorganic base to partially neutralize the acidic media. The process allows obtaining diosmin with low iodine or bromine content, avoiding the use of organic solvents. 1. Process for the preparation of diosmin from hesperidin comprising the following steps:a) acylating hesperidin with the anhydride of a C2-C4 carboxylic acid;b) treating the mixture obtained in step a) with a halogen selected from iodine and bromine, in aqueous medium;c) treating the mixture obtained in step b) with an inorganic base to reach a pH value in the range 3.5-6.5;d) deacylating the acylated diosmin obtained in step c) by treatment with an inorganic base;wherein no organic solvent is added throughout the process.2. Process according to claim 1 , wherein in step a) a catalyst is used selected from sodium acetate and potassium acetate.3. Process according to claim 1 , wherein the anhydride of the C2-C4 carboxylic acid of step a) is acetic anhydride.4. Process according to claim 1 , wherein step b) is carried out bya) using the halogen in a stoichiometric amount, orb) using a halide in a stoichiometric amount and an oxidant in a stoichiometric amount, orc) using the halogen in a catalytic amount and an oxidant in a stoichiometric amount.5. Process according to claim 1 , wherein step b) is carried out by using a halide in a catalytic amount and an oxidant in a stoichiometric amount.6. Process according to claim 4 , wherein the oxidant is selected from the group of hydrogen peroxide claim 4 , sodium percarbonate claim 4 , potassium percarbonate claim 4 , sodium perborate claim 4 , potassium perborate claim 4 , sodium permanganate claim 4 , potassium permanganate claim 4 , sodium dichromate claim 4 , potassium dichromate claim 4 , and hydrates thereof.7. Process ...

PROCESS FOR PERPARING FONDAPARINUX SODIUM AND INTERMEDIATES USEFUL IN THE SYNTHESIS THEREOF

Processes for the synthesis of the Factor Xa anticoagulent Fondaparinux, and related compounds are described. Also described are protected pentasaccharide intermediates as well as efficient and scalable processes for the industrial scale production of Fondaparinux sodium by conversion of the protected pentasaccharide intermediates via a sequence of deprotection and sulfonation reactions. 139-. (canceled)4349-. (canceled) This application is a continuation of U.S. patent application Ser. No. 13/618,786, filed Sep. 14, 2012, which is a continuation of U.S. patent application Ser. No. 12/847,719, filed Jul. 30, 2010, now U.S. Pat. No. 8,288,515, which claims the benefit of U.S. Provisional Application No. 61/230,557, filed Jul. 31, 2009, each of which is incorporated herein by reference in its entirety.The present invention relates to processes for the synthesis of the Factor Xa anticoagulent Fondaparinux, and related compounds. The invention also relates to protected pentasaccharide intermediates and to an efficient and scalable process for the industrial scale production of Fondaparinux sodium by conversion of the protected pentasaccharide intermediates via a sequence of deprotection and sulfonation reactions.In U.S. Pat. No. 7,468,358, Fondaparinux sodium is described as the “only anticoagulant thought to be completely free of risk from HIT-2 induction.” The biochemical and pharmacologic rationale for the development of a heparin pentasaccharide in 86(1), 1-36, 1997 by Walenga et al. cited the recently approved synthetic pentasaccharide Factor Xa inhibitor Fondaparinux sodium. Fondaparinux has also been described in Walenga et al., , Vol. 11, 397-407, 2002 and Bauer, & , Vol. 17, No. 1, 89-104, 2004.Fondaparinux sodium is a linear octasulfated pentasaccharide (oligosaccharide with five monosaccharide units) molecule having five sulfate esters on oxygen (O-sulfated moieties) and three sulfates on a nitrogen (N-sulfated moieties). In addition, Fondaparinux contains ...

STABILISATION OF RADIOPHARMACEUTICAL PRECURSORS

The present invention relates to a method for improving stability of non fluoridated sugar derivatives, and in particular glucose derivatives such as 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-β-D-mannopyranose which are used as precursors for production of radiofluoridated sugar derivatives for use in in vivo imaging procedures such as positron emission tomography (PET). The method comprises storing the non fluoridated sugar derivative in an organic solvent. The resultant formulations of the non fluoridated sugar derivative and cassettes for automated synthesis apparatus comprising the same are also claimed. 1. A method for improving stability of a non fluoridated sugar derivative which comprises storage of said non fluoridated sugar derivative in a solvent in a sealed container.2. A method according to wherein the non fluoridated sugar derivative is a monosaccharide sugar in which one of the OH groups is replaced by a leaving group and the other OH groups of the sugar are each optionally protected with a suitable protecting group.4. A method according to wherein the non fluoridated sugar derivative is 1 claim 1 ,3 claim 1 ,4 claim 1 ,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-β-D-mannopyranose.5. A method according to wherein the solvent is an aprotic solvent.6. A method according to wherein the aprotic solvent is acetonitrile.7. A method according to wherein the solvent has a water content of 1000 ppm or less.8. A method according to wherein the solvent has a water content of between 1000 ppm and 50000 ppm.9. A method according to wherein the sealed container is a septum-sealed vial.10. A formulation of a non fluoridated sugar derivative as defined in comprising said non fluoridated sugar derivative claim 1 , and a solvent in a sealed container.11. A formulation according to wherein the solvent is an aprotic solvent claim 10 , suitably acetonitrile.12. A formulation according to wherein the solvent has a water content of 1000 ppm or less.13. A ...

SYNTHETIC VACCINES AGAINST STREPTOCOCCUS PNEUMONIAE SEROTYPE 2

The present invention relates to a synthetic saccharide of general formula (I) that is related to serotype 2 capsular polysaccharide, a conjugate thereof and the use of said saccharide and conjugate for raising a protective immune response in a human and/or animal host. Furthermore, the synthetic saccharide of general formula (I) is useful as marker in immunological assays for detection of antibodies against type 2 bacteria. 2. The saccharide according to claim 1 , wherein x represents 1 claim 1 , or a pharmaceutically acceptable salt thereof.7. The intermediate of general formula (V) according to claim 6 , wherein P claim 6 , Pand Prepresent a benzyl group claim 6 , P claim 6 , Pand Pare independently of each other selected from benzoyl and acetyl group claim 6 , and Prepresents a benzyloxy carbonyl group.8. A conjugate comprising a saccharide of general formula (I) according to covalently linked to an immunogenic carrier through the nitrogen atom of the —O-L-NHgroup.10. A saccharide according to for use in raising a protective immune response in a human and/or animal host.11Streptococcus pneumoniae. A saccharide according to for use in the prevention and/or treatment of a disease caused by type 2.12. A vaccine comprising the saccharide and/or the pharmaceutically acceptable salt thereof according to together with at least one pharmaceutically acceptable adjuvant and/or excipient.13Streptococcus pneumoniaeStreptococcus pneumoniaeStreptococcus pneumoniaeStreptococcus pneumoniaeStreptococcus pneumoniaeStreptococcus pneumoniae. The vaccine composition according to claim 12 , further comprising at least a capsular polysaccharide of and/or a fragment of a capsular polysaccharide of and/or a conjugate of a carrier protein and a capsular polysaccharide of or a fragment of a capsular polysaccharide of claim 12 , wherein is selected from the group comprising type 1 claim 12 , 3 claim 12 , 4 claim 12 , 5 claim 12 , 6A claim 12 , 6B claim 12 , 7F claim 12 , 8 claim 12 , 9N ...

PURIFIED REBAUDIOSIDE A

The invention provides a high throughput, high purity, high yield system and method of isolating and purifying rebaudioside A (“Reb A”), with acceptable water solubility for all commercial uses, from commercially available starting material. The invention also provides a means of maximizing yields of 99+% purity Reb A based on the attributes of a given batch of starting material. The purity of the Reb A final product, up to 99+% purity, can be selected based on a starting material assay. 1. An alcohol adduct of purified rebaudioside A , that is devoid of bitterness or aftertaste.2. The alcohol adduct of claim 1 , wherein the alcohol adduct is obtained by resolving purified rebaudioside A in an alcohol solvent; the alcohol solvent contains water and alcohol.3. The alcohol adduct of claim 2 , wherein the alcohol is selected from the group consisting of methanol claim 2 , ethanol claim 2 , propanol claim 2 , isopropanol claim 2 , n-butanol claim 2 , sec-butanol claim 2 , isobutanol claim 2 , tert-butanol claim 2 , n-pentanol claim 2 , sec-pentanol claim 2 , isopentanol claim 2 , and neopentanol.4. The alcohol adduct of claim 3 , wherein claim 3 , the alcohol is ethanol.5. The alcohol adduct of claim 1 , wherein claim 1 , the alcohol adduct is in crystal form.6. The alcohol adduct of claim 5 , characterized in that claim 5 , there are diffraction peaks at 20 values of about 4.6 claim 5 , 8.9 claim 5 , 11.9 claim 5 , 13.5 claim 5 , 14.0 claim 5 , 15.2 and 19.1 in a PXRD pattern.7. The alcohol adduct of claim 1 , wherein claim 1 , the alcohol adduct has a melting point of from about 242° C. to about 244° C.8. A product comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a sweetener composition comprising at least 95% by weight on a dry basis of the alcohol adduct of , wherein the product is selected from the group consisting of food, beverage, pharmaceutical composition, tobacco, nutraceutical, oral hygienic composition, or cosmetic.'}9. The product according to ...

OLIGOSACCHARIDE C-GLYCOSIDE DERIVATIVES

The present invention provides a novel process for preparing an oligosaccharide C-glycoside derivative of formula I, comprising reacting a compound of formula II with compound of formula III in the presence of at least one primary or secondary amine and at least one additive [in the formulae, the substituents are as defined herein], and novel oligosaccharide C-glycoside derivatives that can be prepared using the process. 5. The process according to claim 1 , wherein the at least primary or secondary amine and the at least one additive are selected from the group consisting of:{'sub': 3', '3, '(a) pyrrolidine and HBO,'}{'sub': '3', '(b) pyrrolidine and B(OMe), and'}{'sub': 3', '3, '(c) benzylamine and HBO.'}7. The compound according to or a salt thereof claim 6 , wherein the compound is of formula I-1 claim 6 , I-1′ claim 6 , or I-2.9. A pharmaceutical composition claim 6 , comprising the compound according to or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.10. The process according to claim 2 , wherein the at least primary or secondary amine and the at least one additive are selected from the group consisting of:{'sub': 3', '3, '(a) pyrrolidine and HBO,'}{'sub': '3', '(b) pyrrolidine and B(OMe), and'}{'sub': 3', '3, '(c) benzylamine and HBO.'}11. The process according to claim 3 , wherein the at least primary or secondary amine and the at least one additive are selected from the group consisting of:{'sub': 3', '3, '(a) pyrrolidine and HBO,'}{'sub': '3', '(b) pyrrolidine and B(OMe), and'}{'sub': 3', '3, '(c) benzylamine and HBO.'}12. The process according to claim 4 , wherein the at least primary or secondary amine and the at least one additive are selected from the group consisting of:{'sub': 3', '3, '(a) pyrrolidine and HBO,'}{'sub': '3', '(b) pyrrolidine and B(OMe), and'}{'sub': 3', '3, '(c) benzylamine and HBO.'}13. A pharmaceutical composition claim 7 , comprising the compound according to or a pharmaceutically acceptable ...

CATALYTIC GLYCOSYLATION WITH DESIGNER THIOGLYCOSIDE AND NOVEL PROTECTING GROUPS FOR SAME AND FOR SYNTHESIS OF OLIGOSACCHARIDES

A catalytic glycosylation method comprising: installing thioether to an anomeric carbon of a carbohydrate; and catalytically activating the thioether with a non-oxophilic Lewis acid. The thioether may comprise an anomerically stable thioether leaving group. The catalytic glycosylation method may further comprise: utilizing an acid-sensitive ester protecting group as permanent protecting group or using a reactivity-based one-pot glycosylation that employs a single-component catalyst to accelerate an oligosaccharide assembly process. A protecting group to mask hydroxyl functionalities in the production of oligosaccharides, natural products or any molecule having a hydroxyl group comprising an acid-labile ester protecting group. 1. A catalytic glycosylation method comprising:installing thioether to an anomeric carbon of a carbohydrate; andcatalytically activating the thioether with a non-oxophilic Lewis acid.2. The catalytic glycosylation method of wherein the thioether comprises an anomerically stable thioether leaving group.3. The catalytic glycosylation method of further comprising: utilizing an acid-sensitive ester protecting group as permanent protecting group.4. The catalytic glycosylation method of further comprising: using a reactivity-based one-pot glycosylation that employs a single-component catalyst to accelerate an oligosaccharide assembly process.5. The catalytic glycosylation method of further comprising: utilizing an application of a 100%-PEG-based polymer as insoluble support for solid-phase oligosaccharide synthesis.6. The catalytic glycosylation method of further comprising: utilizing a designer thioglycoside that retains basic properties of a parental thioglycoside claim 1 , including the ease of preparation and toleration of backbone protecting group manipulation.7. The catalytic glycosylation method of further comprising: applying an activator permitting an application of highly acid-sensitive protecting groups;applying a 100%-PEG-based polymer as ...

Nucleic Acid Amplification

Methods and compositions for the amplification of nucleic acids and generation of concatemers are disclosed. Amplification methods provided herein may be performed under isothermal conditions. Methods and compositions may include reagents such nucleic acid polymerases and primers. 135-. (canceled)36. A method of copying a polynucleotide template , the method comprising:(A) annealing a nucleic acid comprising the polynucleotide template to a first primer, wherein: the polynucleotide template comprises in the 5′ to 3′ direction a second nucleotide sequence and a first nucleotide sequence; and the first primer comprises in the 5′ to 3′ direction a first nucleotide sequence and a second nucleotide sequence, wherein the second nucleotide sequence of the first primer comprises a nucleotide sequence which is complementary to the first nucleotide sequence-of the polynucleotide template;(B) synthesizing a first extension product from the first primer in the presence of a polymerase;(C) annealing a second primer to the first extension product, wherein the second primer comprises in the 5′ to 3′ direction a first nucleotide sequence and a second nucleotide sequence, wherein the second nucleotide sequence of the second primer comprises a nucleotide sequence which is complementary to a partner nucleotide sequence, wherein the partner nucleotide sequence is a nucleotide sequence complementary to the second nucleotide sequence of the polynucleotide template, wherein the first nucleotide sequence of the first and second primers are complementary to each other;(D) synthesizing a second extension product from the second primer in the presence of the polymerase;(E) annealing the first primer to the 3′ end of the second extension product and synthesizing a third expression product from the first primer in the presence of the polymerase;(F) generating a double-stranded nucleic acid comprising the third extension product and the second extension product;(G) repeating at least steps (E)-( ...

Processes and Materials for the Synthesis of Sugar Esters Found in Natural Tobacco

A process and materials method for making a glucose tetraester may include reacting glucose with a carboxylic acid to create a glucose pentaester. The glucose pentaester was reacted with a basic reagent to create a glucose tetraester. Glucose was reacted with a carboxylic acid anhydride in the presence of 4-dimethylaminopyridine to create a glucose pentaester product. The glucose pentaester reaction product was separated. The glucose pentaester reaction product was reacted with a basic reagent, wherein the reaction steps may take place at a temperature of about 0° C. to about 60° C. and about ambient pressure, wherein the ratio of the carboxylic acid to the glucose was from about 5:1 to about 50:1, and wherein the ratio of the glucose pentaester to the basic reagent was from about 1:50 to about 1:150.

BIOMASS DIGESTER WITH TWO LIQUID PHASES AND DRAFT TUBE CIRCULATION

A method comprises introducing biomass solids to a digester comprising a reactor, a circulation system including a first injector; providing a catalyst-containing digestion medium and an organic solvent layer floating thereon; circulating the medium through the circulation system; flowing gas through the medium; keeping the medium hot enough to digest the solids; and operating the digester such a headspace exists above the solvent. The digester includes a first eductor having an inlet in the headspace, a second eductor having an inlet in the organic layer, and a downdraft tube having an inlet in the digestion medium. A motive fluid flowing from the first injector draws gas from the headspace into the first eductor, a motive fluid flowing from the first eductor draws fluid from the organic layer into the second eductor, and a motive fluid flowing from the second eductor draws fluid from the digestion medium into the downdraft tube. 1. A method comprising: i) a reactor;', 'ii) a gas feed line for providing gas to the reactor;', 'iii) a biomass feed system for feeding biomass into the reactor;', 'iv) a fluid circulation system including a fluid inlet, a pump, and at least one fluid injector, wherein at least said fluid inlet and said fluid injector are in fluid communication with said pump and are within said reactor; and', 'v) a screen positioned within the reactor and defining a lower zone therebelow;, 'a) introducing cellulosic biomass solids to a hydrothermal digestion unit comprisingb) providing a liquid phase digestion medium containing a slurry catalyst in the hydrothermal digestion unit, the slurry catalyst being capable of activating molecular hydrogen;c) providing a layer of organic solvent in the hydrothermal digestion unit, said organic solvent being less dense than and substantially immiscible with said digestion medium, whereby said organic solvent forms an organic layer floating on said digestion medium;d) circulating said liquid phase digestion medium ...

Rhamnolipid Amides For Hair Scent Retention

The invention provides derivatives of rhamnolipids, formulations comprising these, and the use thereof. 1. A rhamnolipid amide.3. The rhamnolipid amide according to claim 2 , wherein Ris selected from the group consisting of the alkyl radicals.5. The rhamnolipid amide according to claim 2 , wherein the radical —NRRis derived from an amine NHRRselected from amino acids and peptides.6. A process for the preparation of rhamnolipid amides comprising the process stepsA) providing a rhamnolipid,B) reacting the rhamnolipid with at least one coupling reagent,C) reacting the rhamnolipid activated by process step B) with an amine, and optionallyD) purifying ourthe rhamnolipid amide.7. The process according to claim 6 , wherein in process step B) the coupling reagent used is at least one selected from the group consisting on dicyclohexylcarbodiimide claim 6 , diisopropylcarbodiimide claim 6 , 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride claim 6 , N-cyclohexyl-N′-(2′-morpholinoethyl)carbodiimide metho-p-toluenesulphonate claim 6 , N-benzyl-N′-3′ dimethylaminopropylcarbodiimide hydrochloride claim 6 , 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide claim 6 , N-ethylcarbodiimide hydrochloride and carbonyldiimidazole.8. The process according to claim 6 , wherein in process step C) at least one catalyst selected from the the group consisting of N-ethyldiisopropylamine claim 6 , trialkylamines claim 6 , pyridine claim 6 , 4-dimethylaminopyridine and hydroxybenzotriazole.9. The rhamnolipid amide obtainable by a process according to .10. A formulation claim 1 , in particular a cosmetic one claim 1 , comprising at least one rhamnolipid amide according to .11. A hair fragrance comprising the rhamnolipid amide according to .12. The rhamnolipid amide according to claim 2 , wherein Ris selected from the group consisting of the alkyl radicals having amine groups and having 4 to 8 carbon atoms.13. The rhamnolipid amide according to claim 2 , wherein Ris H.14. The rhamnolipid ...

METHODS, DEVICES, AND KITS TO IMPROVE REDUCTION OR LABELING OF CARBOHYDRATES

The present invention provides methods, devices, and kits to improve procedures for reducing carbohydrates, such as glycans released from glycoconjugates, or for labeling carbohydrates by reductive amination. 2. The method of claim 1 , further comprising step e′ claim 1 , washing any excess reductant or label from said first porous solid support using organic solvent or a solution with a concentration of organic solvent higher than 95% organic solvent following said reduction or labeling.3. The method of claim 2 , further comprising step e″ claim 2 , eluting said washed reduced or labeled carbohydrates from said first porous solid support using an aqueous solution comprising up to 20% organic solvent following said wash.4. The method of claim 3 , wherein said aqueous solution comprising up to 20% organic solvent comprises water or a buffer solution.5. The method of claim 3 , wherein said aqueous solution does not comprise any organic solvent.6. The method of claim 1 , wherein said first porous solid support is made of a hydrophilic material or has a hydrophilic material claim 1 , other than one bearing carboxyl groups claim 1 , on its surface.7. The method of claim 1 , wherein said first porous solid support is made of a hydrophilic material.8. The method of claim 6 , wherein said hydrophilic material is (a) cellulose claim 6 , (b) glass claim 6 , (c) alumina claim 6 , (d) silica claim 6 , (e) a functionalized surface containing diol claim 6 , aminopropyl claim 6 , carbamoyl claim 6 , cyanopropyl claim 6 , ethylenediamine-N-propyl claim 6 , (f) silica derivatized with diol claim 6 , aminopropyl claim 6 , or carbamoyl claim 6 , (g) a porous hydrophilic material other than one bearing one or more carboxyl groups claim 6 , or (h) a combination of two or more of these.9. The method of claim 8 , wherein said glass is glass fiber.10. The method of claim 1 , wherein said first porous solid support is made of a non-hydrophilic material or has a surface of non-hydrophilic ...

GLYCOCONJUGATES AND USE THEREOF AS VACCINE AGAINST SHIGELLA FLEXNERI SEROTYPE 3a AND X

The present invention relates to compounds derived from sugars which reproduce the epitopes of serotypes 3a and X and to the use thereof for the preparation of vaccine compositions. More specifically, the subject matter of the present invention relates to novel glycoconjugated compounds comprising oligosaccharides or polysaccharides described hereinafter, to the method for synthesizing these oligosaccharides or polysaccharides and glycoconjugates, to derivatives of these oligosaccharides or polysaccharides, to compositions containing same, and also to the use of the glycoconjugates for vaccination purposes. Finally, the present invention relates to methods for diagnosing a infection using one or more oligosaccharides or polysaccharides or conjugates thereof. 111-. (canceled)14Shigella flexneri. A kit for diagnosis of an infection with of serotype 3a or X claim 12 , wherein it comprises at least one saccharide as claimed in .15. A method of preparation of the disaccharide (E)A (I) claim 12 , an intermediate in the synthesis of a saccharide as defined in claim 12 , wherein it comprises the following stages:condensation of the acceptor monosaccharide 31 with the donor monosaccharide 33 leading to the disaccharide 35;deacetylation of the disaccharide 35 to give the disaccharide 21; anddeprotection of the disaccharide 21 by hydrogenolysis of the benzyl groups to give the disaccharide (E)A.16. A method of preparation of the trisaccharide D(E)A (II) claim 12 , as defined in claim 12 , wherein it comprises the following stages:condensation of the donor monosacccharide 1 with the acceptor disaccharide 21 leading to the trisaccharide 22;deacetylation of the trisaccharide 22 leading to the trisaccharide 37; anddeprotection of the trisaccharide 37 to give the trisaccharide D(E)A.17. A method of preparation of the trisaccharide D(E)A (II) claim 12 , as defined in claim 12 , comprising the following stages:condensation of the donor monosacccharide 2 with the acceptor disaccharide ...

METHOD AND DEVICE FOR PRODUCING SACCHARIDES AND SACCHARIDE ARRAYS

The present invention relates to a method and a device for producing saccharides and saccharide arrays. Said method is particularly useful for the synthesis of saccharides in parallel and of high-density saccharide arrays, such as microarrays, which are required for high-throughput screenings. 1. A method for synthesizing saccharide comprising the steps:A) providing a solid support with at least one immobilized acceptor group for reacting with a saccharide;B) delivering the saccharide onto the solid support;C) applying a vapor of a mixture of a glycosylation reagent and a solvent onto the solid support at a temperature below 20° C. in order to initiate a coupling reaction of the saccharide to the at least one immobilized acceptor group.2. The method according to claim 1 , wherein step C) is carried out at a temperature below 5° C.3. The method according to claim 1 , wherein the ratio of the solvent and the glycosylation reagent is in the range of 1:10 to 100 claim 1 ,000:1.4. The method according to claim 1 , wherein the solvent is an aprotic organic solvent selected from: methylene chloride claim 1 , chloroform claim 1 , acetonitrile claim 1 , diethyl ether claim 1 , 1 claim 1 ,4-dioxane claim 1 , methyl tert-butyl ether claim 1 , toluene and ethyl acetate.5. The method according to claim 1 , wherein the glycosylation reagent is a Lewis acid selected from: AgOTf claim 1 , BF.OEt claim 1 , trimethylsilyl trifluoromethanesulfonate claim 1 , trifluoromethanesulfonic acid claim 1 , trifluoromethanesulfonic anhydride claim 1 , lanthanoid(III) triflates claim 1 , NIS/AgOTf claim 1 , NIS/TfOH or dimethyl(methylthio)sulfonium trifluoromethanesulfonate.7. The method according to claim 1 , wherein in step B) the saccharide is a monosaccharide.8. The method according to claim 1 , further comprising step C′) between step B) and step C):C′) drying the solid support obtained in step B) under reduced pressure and/or heating.9. The method according to claim 1 , further comprising ...

HYDRATED AND ANHYDROUS POLYMORPHS OF 2'-O-FUCOSYLLACTOSE AND THEIR PRODUCTION METHODS

This invention describes new hydrated and anhydrous polymorphs of 2′-0-ficosyllactose (2′FL): Polymorph A 2′FL-3/2HO, Polymorph B 2TL-5/2HO and anhydrous Polymorph C. There is also a description of the methods for obtaining them, and of a new method for preparing Polymorph I already known in the literature. 116.-. (canceled)17. 2′-O-Fucosyllactose (2′FL) in anhydrous crystalline form of polymorph C , wherein said polymorph C has characteristic XRPD peaks at 17.58±0.20 , 17.44±0.20 , 10.63±0.20 2Θ.18. A polymorph C according to claim 17 , having characteristic XRPD peaks at 17.58±0.20 claim 17 , 17.44±0.20 claim 17 , 10.63±0.20 claim 17 , 5.30±0.2 claim 17 , 20.05±0.20 2Θ.19. A polymorph C according to claim 17 , wherein the single crystal is arranged within a monocline system and the elementary cell has the following parameters: a=5.058(1) Å claim 17 , b=12.773(3) Å claim 17 , c=16.692(5) Å and a volume of 1074.75 Å.20. A method for preparing the polymorph C according to claim 17 , the method comprising crystallizing 2′FL from a C-Calcohol or mixtures thereof.21. A method for preparing the polymorph I claim 17 , having an X-ray powder diffraction with characteristic peaks at angles 2Θ 21.34±0.20° claim 17 , 20.92±0.20° claim 17 , 18.37±0.20° claim 17 , 16.70±0.20° claim 17 , 9.91±0.20° claim 17 , 13.13±0.20° claim 17 , 7.87±0.20° and 8.90±0.20° claim 17 , said method comprising the crystallization from glacial acetic acid.2223.-. (canceled)24. A method for obtaining crystalline 2′-O-Fucosyllactose (2′FL) anhydrate in form of polymorph C with molecular formula CHO claim 17 , the method comprising:{'sub': 1', '3', '18', '32', '15', '2, 'providing a mixture comprising (i) a C-Calcohol or mixture thereof and (ii) a 2′FL hydrate in form of polymorph A with molecular formula CHO.nHO wherein n is 3/2; and'}warming the mixture at a temperature in range of 30° C. to 70° C. for 1 hr to 24 hr, thereby crystallizing the 2′FL and forming 2′FL anhydrate in form of polymorph C ...

HYDRATED AND ANHYDROUS POLYMORPHS OF 2'-O-FUCOSYLLACTOSE AND THEIR PRODUCTION METHODS

This invention describes new hydrated and anhydrous polymorphs of 2′-O-fucosyllactose (2′FL): Polymorph A 2′FL-3/2HO, Polymorph B 2TL-5/2 HO and anhydrous Polymorph C. There is also a description of the methods for obtaining them, and of a new method for preparing Polymorph I already known in the literature. 123.-. (canceled)24. A method for obtaining crystalline 2′-O-Fucosyllactose (2′FL) , the method comprising:providing 2′FL in an aqueous solution comprising (i) water and (ii) the 2′FL dissolved therein;adding a crystallization solvent to the aqueous solution over a period of 1 hr to 15 hr, thereby crystallizing the 2′FL and forming 2′FL crystals suspended in the aqueous solution;separating the 2′FL crystals from the aqueous solution to collect solid 2′FL crystals; anddrying the solid 2′FL crystals.25. The method of claim 24 , wherein providing the aqueous solution comprises dissolving in the water a 2′FL hydrate in form of polymorph A with molecular formula CHO.nHO wherein n is 3/2.26. The method of claim 24 , wherein providing the aqueous solution comprises dissolving in the water a 2′FL form selected from the group consisting of 2′FL polymorph A claim 24 , 2′FL polymorph B claim 24 , 2′FL polymorph C claim 24 , 2′FL polymorph I claim 24 , 2′FL polymorph II claim 24 , amorphous 2′FL claim 24 , and combinations thereof.27. The method of claim 24 , further comprising:performing a synthesis procedure selected from the group consisting of extraction, enzymatic synthesis, chemical synthesis, and combinations thereof to obtain the 2′FL that is then dissolved in the water to provide the aqueous solution.28. The method of claim 24 , wherein the aqueous solution is in the form or a syrup having a 2′FL concentration in a range of 50 wt. % to 80 wt. %.29. The method of claim 24 , wherein the crystallization solvent is selected from the group consisting of alcohols claim 24 , ketones claim 24 , nitriles claim 24 , organic acids claim 24 , esters claim 24 , and combinations ...

Process for the Preparation of ß-C-Aryl Glucosides

The present invention provides processes for stereoselectively preparing C-arylglucosides that can be useful as synthetic building block or drugs, including SGLT2 inhibitors. 2. A process in accordance with claim 1 , wherein said metalated aryl compound represented by the formula [ArMY]M claim 1 , whereinAr is a member selected from the group consisting of an aromatic ring, an aromatic heterocyclic ring, a biaryl ring system, a fused aromatic ring, a polyaromatic system, two or more aromatic rings bridged by a methylene group, and a meta-substituted diarylmethane system;{'sup': '1', 'Mis selected from the group consisting of metals, metalloids, poor metals, alkaline earth metals, and lanthanides;'}{'sup': '1', 'Yis not present, or is one or more anions independently selected from the group consisting of halides, phenoxides, alkoxides, sulfonates, sulfates, carboxylates, carbanions, cyanide and cyanate;'}{'sup': '2', 'Mis not present, or is one or more cations;'}the subscript n is an integer or a non-integer number from 1 to 6;the subscript p is an integer or a non-integer number from 0 to 6, and n+p is the total number of anions;the subscript q is an integer or a non-integer number from 0 to 4, and is the total number of cations; and{'sup': 3', '2', '3', '2, 'sub': 'r', 'wherein the process is optionally carried out in the presence of metallic or non-metallic Lewis acid MY, wherein Mis a metal, a metalloid or a non-metal; Yis an anion; and the subscript r is an integer of from 1 to 7.1'}7. The process according to claim 6 , wherein the metalated aryl compound is represented by the formula [ArMY]M claim 6 , whereinAr is a member selected from the group consisting of an aromatic ring, an aromatic heterocyclic ring, a biaryl ring system, a fused aromatic ring, a polyaromatic system, two or more aromatic rings bridged by a methylene group, and a meta-substituted diarylmethane system;{'sup': '1', 'Mis selected from the group consisting of metals, metalloids poor metals, ...

Compositions and Methods for the Inhibition of Methyltransferases

Methods and compositions disclosed herein relate to detecting, analyzing, isolating and inhibiting methyltransferases, methyltransferase substrates, S-adenosyl-methionine-binding proteins and RNA, including for the treatment of disease. 2. The compound of claim 1 , wherein Ris selected from the group consisting of adenosine claim 1 , deoxyadenosine claim 1 , guanosine claim 1 , deoxyguanosine claim 1 , 5-methyluridine claim 1 , thymidine claim 1 , uridine claim 1 , deoxyuridine claim 1 , cytidine claim 1 , deoxycytidine claim 1 , formycin claim 1 , aristeromycin claim 1 , didanosine claim 1 , inosine claim 1 , acyclovir claim 1 , deoxyinosine claim 1 , abacavir claim 1 , N4-acetylcytidine claim 1 , allopurinol riboside claim 1 , 2′-O-allyladenosine claim 1 , 3′-O-allyladenosine claim 1 , 3′-O-allylcytidine claim 1 , 2′-O-allylcytidine claim 1 , 2′-O-allylguanosine claim 1 , 3′-O-allylguanosine claim 1 , 2′-O-allyluridine claim 1 , 3′-O-allyluridine claim 1 , bromodeoxyuridine claim 1 , cytarabine claim 1 , azacitidine claim 1 , decitabine claim 1 , pseudouridine claim 1 , S-adenosyl-L-homocysteine claim 1 , pentostatin claim 1 , regadenoson claim 1 , telbivudine claim 1 , 8-oxo-2′-deoxyguanosine claim 1 , CGS-21680 claim 1 , floxuridine claim 1 , 5-methyluridine claim 1 , dihydrouridine claim 1 , nelarabine claim 1 , xanthosine claim 1 , maribavir claim 1 , 8-hydroxyguanosine claim 1 , N4-chloroacetylcytosine arabinoside claim 1 , sapacitabine claim 1 , orotidine claim 1 , queuosine claim 1 , lysidine claim 1 , fialuridine claim 1 , CP-532 claim 1 ,903 claim 1 , cordycepin claim 1 , tezacitabine claim 1 , dexelvucitabine claim 1 , N6-cyclopentyladenosine claim 1 , iododeoxyuridine claim 1 , PSI-6130 claim 1 , 5 claim 1 ,6-dichloro-1-beta-D-ribofuranosylbenzimidazole claim 1 , S-adenosylmethioninamine claim 1 , FV-100 and 5-ethynyl-2′-deoxyuridine claim 1 , 9-β-D-allopyranosyl-9H-Purin-6-amine claim 1 , (S)-9-(2 claim 1 ,3-dihydroxypropyl)adenine (DHPA) claim 1 , D- ...

SYNTHETIC MEMBRANE ANCHORS

A construct of the structure F—S-Swhere: F—Sis an aminoalkylglycoside where F is α-D-galactopyranosyl-()-B-D-galactopyranosyl-()-β-D-glucopyranoside and Sis 2-aminoethyl, 3-aminopropyl, 4-aminobutyl or 5-aminopentyl; Sis —CO(CH)CO—, —CO(CH)CO—, —CO(CH)CO— or —CO(CH)CO—; and L is phosphatidylethanolamine. 1) A construct of the structure F—S-S-L where: F—Sis an aminoalkylglycoside where F is α-D-galactopyranosyl-(1→4)-β-D-galactopyranosyl-(1→4)-β-D-glucopyranoside and Sis 2-aminoethyl , 3-aminopropyl , 4-aminobutyl or 5-aminopentyl; Sis —CO(CH)CO— , —CO(CH)CO— , —CO(CH)CO— or —CO(CH)CO—; and L is phosphatidylethanolamine.2) The construct of where Sis 2-aminoethyl claim 1 , 3-aminopropyl.3) The construct of where Sis —CO(CH)CO—.4) The construct of where L is dioleoylphosphatidylethanolamine. The invention relates to synthetic molecules that spontaneously and stably incorporate into lipid bi-layers, including cell membranes. Particularly, although not exclusively, the invention relates to the use of these molecules as synthetic membrane anchors or synthetic molecule constructs to effect qualitative and quantitative changes in the expression of cell surface antigens.Cell surface antigens mediate a range of interactions between cells and their environment. These interactions include cell-cell interactions, cell-surface interactions and cell-solute interactions. Cell surface antigens also mediate intra-cellular signalling.Cells are characterised by qualitative and quantitative differences in the cell surface antigens expressed. Qualitative and quantitative changes in the cell surface antigens expressed alter both cell function (mode of action) and cell functionality (action served).Being able to effect qualitative and/or quantitative changes in the surface antigens expressed by a cell has diagnostic and therapeutic value. Transgenic and non-transgenic methods of effecting qualitative and/or quantitative changes in the surface antigens expressed by a cell are known.Protein ...

Trisaccharide Derivates, and Their Use as Adjuvants

The present invention relates to the use of trisaccharide derivates comprising a substituted trisaccharide core, which trisaccharide core is fully substituted with fatty acid ester groups, and optionally one or more anionic groups as adjuvants, to the trisaccharide derivates as such, to a method for preparing such trisaccharides, to trisaccharides obtained with such method, to adjuvant compositions comprising such trisaccharide derivates and to a vaccine or kit comprising such adjuvant compositions. 110-. (canceled)11. A trisaccharide derivate comprising a substituted trisaccharide core , which trisaccharide core is fully substituted with fatty acid ester groups , and optionally one or more anionic groups as an adjuvant.12. The trisaccharide derivate according to claim 11 , wherein the substituted trisaccharide core is derived from raffinose claim 11 , melezitose claim 11 , maltotriose claim 11 , nigerotriose claim 11 , maltotriulose or kestose.13. The trisaccharide derivate according to claim 11 , wherein the substituted trisaccharide core comprises one or two sulphate ester or phosphate ester groups as anionic groups.14. The trisaccharide derivate according to claim 11 , wherein the anionic group is a sulphate ester.15. The trisaccharide derivate according to claim 11 , wherein the fatty acid ester group is an ester of a straight claim 11 , branched claim 11 , saturated or unsaturated fatty acid with a chain length of 4 to 20 carbon atoms.16. The trisaccharide derivate according to claim 11 , wherein the fatty acid ester is the ester of lauric acid claim 11 , myristic acid claim 11 , palmitic acid claim 11 , stearic acid or arachidic acid.17. The trisaccharide derivate according to claim 11 , wherein the fatty acid ester groups of the substituted trisaccharide core are all identical.18. The trisaccharide derivate according to claim 11 , wherein the substituted trisaccharide core is derived from raffinose claim 11 , melezitose or maltotriose and wherein the ...

OLIGONUCLEOTIDE SYNTHESIZER

The disclosure provides a new and improved oligonucleotide synthesizer. 1. A process for making an oligonucleotide , comprising reacting a oligonucleotide precursor with a solid phase support , and mechanically stirring the solid phase support.2. The process of claim 1 , further comprising one or more activation steps.3. The process of claim 1 , further comprising one or more coupling steps.4. The process of claim 1 , further comprising one or more capping steps.5. The process of claim 1 , further comprising one or more oxidation steps.6. The process of claim 1 , further comprising one or more detritylation steps.7. The process of claim 1 , further comprising one or more cleavage steps.8. The process of claim 1 , further comprising one or more deprotection steps.9. The process of claim 1 , wherein the solid phase support comprises a plurality of discrete resin pieces.10. The process of claim 9 , wherein the plurality of discrete resin pieces comprises a plurality of resin beads.11. The process of claim 1 , wherein the mechanical stirring of the solid phase support comprises the motion of a reaction vessel comprising the solid support relative to a chassis claim 1 , frame claim 1 , or support.12. The process of claim 11 , wherein the motion comprises one or more of tipping claim 11 , rocking claim 11 , shaking claim 11 , and inverting the reaction vessel relative to the chassis claim 11 , frame claim 11 , or support.13. The process of claim 1 , wherein the mechanical stirring of the solid phase support comprises stirring via a stir blade claim 1 , a stir bar claim 1 , or both.14. The process of claim 1 , wherein the mechanical stirring of the solid phase support comprises stirring via a plurality of bubbles moving relative to the solid phase support.15. The process of claim 9 , wherein the plurality of discrete resin pieces comprise a low cross link resin for high swelling in acetonitrile (ACN) claim 9 , wherein the low cross link resin has a higher substitution ...

DNA GRIDIRON COMPOSITIONS AND METHODS

Novel compositions and methods for engineering wireframe architectures and scaffolds of increasing complexity by creating gridiron-like DNA structures (FIG. ). A series of four-arm junctions are used as vertices within a network of double-helical DNA fragments. Deliberate distortion of the junctions from their most relaxed conformations ensures that a scaffold strand can traverse through individual vertices in multiple directions. DNA gridirons, ranging from two-dimensional arrays with reconfigurability to multilayer and three-dimensional structures and curved objects, can be assembled according the methods presented herein. 19-. (canceled)10. A composition comprising a plurality of immobile Holliday junction analogs linked together in a plurality of layered frames , wherein each layer of frame has at least two DNA helices which lie on opposite sides of the Holliday junction which also lie in the same plane , and wherein said plurality of immobile Holliday junction analogs are linked together with a central strand of single-stranded DNA within said layer of frame.11. The composition of claim 10 , wherein each layer of frame is independently selected from a hexagonal claim 10 , rectangular claim 10 , or parallelogram shape.12. The composition of claim 10 , wherein said plurality of immobile Holliday junction analogs are linked together in a frame having at least three layers.13. The composition of claim 10 , wherein said plurality of immobile Holliday junction analogs are linked together in a frame having at least four layers.14. The composition of claim 10 , wherein said single stranded DNA comprises M13mp18 DNA.15. The composition of claim 10 , wherein the multi-layered frame having at least three layers comprises a lattice defined by the lengths of said lattice claim 10 , and the interstitial space confined by the lattice defines a cavity claim 10 ,wherein the lattice comprises at least three double-stranded DNA strands, each of which has an independent length.16. ...

METHOD FOR PREPARING OLIGOMERIC MANNURONIC DIACID

The invention relates to a new method of preparing oligomannuronic diacids, important bioactives. The method utilizes oligomannuronic acids as starting materials and the target substances are obtained by acid degradation and active hypobromous acid oxidation steps. The method of preparing oligomannuronic diacids according to the invention employs moderate reaction conditions, has few side reactions, does not need further purification, achieves a yield of more than 90%, or even more than 95%, and is suitable for production with an on-line continuous reactor device, with reaction processes easy to implement automatic control. 1. A method of preparing oligomannuronic diacids , comprising an oxidation reaction step of contacting oligomannuronic acids with a bromine-containing oxidant.2. The method of claim 1 , wherein the bromine-containing oxidant is selected from the group consisting of bromine water claim 1 , liquid bromine claim 1 , hypobromous acid claim 1 , hypobromite claim 1 , a combination of a bromide ion source with hypochlorite claim 1 , and a combination of bromine with hypochlorite.3. The method of claim 1 , wherein the molar amount of the bromine-containing oxidant calculated based on hypobromous acid and/or hypochlorite is 1.0-2.0 folds of the reaction raw material oligomannuronic acid.4. The method of claim 1 , wherein the temperature of the oxidation reaction is 10-40° C.5. The method of claim 1 , wherein the pH of the oxidation reaction is controlled to be between 6.5 and 9.5.6. The method of claim 2 , wherein the hypobromous acid or hypobromite is obtained by in situ production.7. The method of claim 6 , wherein the in situ production is achieved by the reaction of bromine with an aqueous alkaline solution.8. The method of claim 1 , wherein the aqueous alkaline solution is an aqueous solution of an alkali metal hydroxide or an alkali metal phosphate or an alkali metal carbonate claim 1 , such as an aqueous solution of sodium hydroxide or sodium ...

Method for preparing 3-o-benzyl-1,2-o-isopropylidene-a-l-furan idose

Provided is a method for preparing 3-O-benzyl-1,2-O-isopropylidene-α-L-idofuranose, which comprises: (1) protecting hydroxyl of 3-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose (III) by benzoyl and methylsulfonyl to obtain 6-O-benzoyl-3-O-benzyl-1,2-O-isopropylidene-5-O-methylsulfonyl-α-D-glucofuranose (V); (2) subjecting compound (V) to a cyclization reaction under an alkaline condition to obtain 5,6-epoxy-3-O-benzyl-1,2-O-isopropylidene-α-L-idofuranose (VI); and (3) subjecting compound (VI) to a ring-opening reaction to obtain 3-O-benzyl-1,2-O-isopropylidene-α-L-idofuranose.

SYNTHESIS OF 1:1:1 CO-CRYSTAL OF 1-CYANO-2-(4-CYCLOPROPYL-BENZYL)-4-(ß-D-GLUCOPYRANOS-1-YL)-BENZENE, L-PROLINE AND WATER

Intermediate compounds are described herein and which are used to manufacture a crystalline compound 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranos-1-yl)-benzene L-proline monohydrate. This application is a divisional of U.S. patent application Ser. No. 16/771,717, filed on Jun. 11, 2020, which is a 35 U.S.C. § 371 national stage application of PCT/EP2018/085193, filed on Dec. 17, 2018, which claims priority to European patent application EP 17208315.6 filed on Dec. 19, 2017, the disclosures of which are hereby incorporated by reference in their entireties.The invention relates to the field of chemistry, particularly synthetic chemistry. In particular, the invention relates to the synthesis of crystalline 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranos-1-yl)-benzene L-proline monohydrate, more particular to the 1:1:1 co-crystal of all three crystal components 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranos-1-yl)-benzene, L-proline and water.WO 2007/093610 describes glucopyranosyl-substituted benzonitrile derivatives, pharmaceutical compositions containing such compounds, their medical uses as well as processes for their manufacture. It discloses among many other compounds also 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranos-1-yl)-benzene.WO 2007/128749 relates to glucopyranosyl-substituted benzonitrile derivatives, pharmaceutical compositions containing such compounds, their medical uses as well as processes for their manufacture. Among many other compounds it also discloses 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranos-1-yl)-benzene.WO 2014/016381 describes crystalline complexes of 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranos-1-yl)-benzene with natural amino acids, methods for the preparation thereof as well as the use thereof for preparing medicaments. Although the WO publication describes crystalline 1-cyano-2-(4-cyclopropyl-benzyl)-4-(O-D-glucopyranos-1-yl)-benzene L-proline it does not explicitly mention 1-cyano-2-(4- ...

NOVEL SYNTHETIC OLIGOMERS OF NEISSERIA MENINGITIS SEROGROUP X AND PROCESS OF PREPARING THEM

The present invention relates to synthesis of novel higher oligomers and process of preparing the same. In particular the present invention relates to the chemical synthesis of oligomers of serogroup X (‘hereinafter Men-X), more particularly tetramer. The present invention provides Men-X capsular oligomers obtained from synthetic pathway using purified saccharides of specific chain length and provides said novel oligomers as candidates for the development of conjugate vaccine against bacterial meningitis caused due to Men-X infections. 1. Novel process of synthesizing oligomers , said process comprising the steps of:synthesizing hemiacetal compd (10)synthesizing propagation unit (12) and terminal unit(s) (14) and (14A)coupling said propagation unit (12) with said terminal unit (14) and coupling said propagation unit (12) with said terminal unit (14A) in the presence of coupling reagents to yield compound (15) and (15A) respectivelyreacting said compounds (15) and (15A) with deacetylating reagents to obtain compounds (16) and (16A) and then coupling compounds (16) and (16A) using said coupling reagents to obtain compounds (17) and (17A)iterative reactions in the presence of said deacetylating reagents and said coupling reagents to yield novel higher synthetic oligomers (18,18A,19,19A,1,1A,X,XA)one step reduction by reductive N-acetylating reagent, deacetylation using said deacetylating reagents and final deprotection of benzyl and Cbz by hydrogenation,such that said process results in novel higher synthetic oligomers (X) and (XA) with better yield, high purity and enhanced efficacy.2. The novel process of synthesizing oligomers as claimed in wherein said novel higher synthetic oligomers (X) and (XA) is tetramer (1) and (1A)3. The novel process of synthesizing oligomers as claimed in wherein the time taken to synthesize said tetramers (1) and (1A) is in the range of 225 hours to 276 hours claim 1 , preferably in 257 hours.4. The novel process of synthesizing oligomers ...

DNA GRIDIRON COMPOSITIONS AND METHODS

Novel compositions and methods for engineering wireframe architectures and scaffolds of increasing complexity by creating gridiron-like DNA structures (FIG. ). A series of four-arm junctions are used as vertices within a network of double-helical DNA fragments. Deliberate distortion of the junctions from their most relaxed conformations ensures that a scaffold strand can traverse through individual vertices in multiple directions. DNA gridirons, ranging from two-dimensional arrays with reconfigurability to multilayer and three-dimensional structures and curved objects, can be assembled according the methods presented herein. 1. A composition , comprising:a plurality of immobile Holliday junction analogs linked together in a two-layer square frame in which the helices on opposite sides lie in the same plane.2. A method of forming a DNA gridiron unit , comprising:combining a plurality of scaffold strands and staple strands complementary to said scaffold strand under conditions suitable for the formation of four four-arm junctions linked together in a two-layer square frame in which the helices on opposite sides lie in the same plane.3. The method of claim 2 , wherein said scaffold strands comprise single stranded M13mp18 DNA.4. The method of claim 2 , wherein said scaffold strands are combined with a 10 times molar excess of staple strands in TAE Mg2+ buffer.5. The method of claim 2 , wherein said scaffold strands and staple strands are annealed from 95° C. to 4° C. for a predetermined time.6. A method of forming a DNA origami nanostructure claim 2 , comprising:linking a number of gridiron units of a predetermined sequence of nucleotides under conditions suitable to form a 2D or 3D lattice of a predetermined design.7. A method of forming a DNA origami nanostructure claim 2 , comprising:designing a plurality of DNA sequences corresponding to a desired shape; andassembling said sequences into at least one gridiron unit.8. The method of claim 7 , wherein said designing ...

REVERSIBLE MODIFICATION OF NUCLEOTIDES

Disclosed herein, inter alia, are methods for modifying a nucleotide, for example including reacting a nucleotide having a 3′-O-oxime moiety with a reagent having the structure R2-ONHto produce a nucleotide having a 3′-O—NHmoiety, wherein R2 is independently alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, or an optionally substituted variant thereof. 1. A method of replacing a protecting group by a blocking group at a 3′ position of a nucleotide , comprising contacting the nucleotide and a reagent comprising the structure R2-block , wherein R2 has a molecular weight of at least 24 , wherein R2-block is water soluble , and wherein block comprises a blocking group moiety.2. The method of claim 1 , wherein block comprises a reversible terminator moiety.3. The method of claim 2 , wherein the reversible terminator moiety does not preclude assembly of a nucleotide reversibly terminated thereby into a ternary complex.4. The method of claim 1 , wherein R2-block is selected from the group consisting of R2-O—NH claim 1 , R2-O—NHCH claim 1 , R2-O—NHCOCH claim 1 , or R2O—CHN.5. The method of claim 4 , wherein R2-block is R2O—CHN.6. The method of claim 4 , wherein R2-block is R2-O—NH.8. The method of claim 4 , wherein the protecting group comprises an —O-oxime.9. The method of claim 8 , wherein the —O-oxime moiety has the formula: —O—N═C(R3)(R4); and R3 and R4 are independently hydrogen claim 8 , substituted or unsubstituted alkyl claim 8 , substituted or unsubstituted alkenyl claim 8 , substituted or unsubstituted alkynyl claim 8 , substituted or unsubstituted heteroalkyl claim 8 , substituted or unsubstituted cycloalkyl claim 8 , substituted or unsubstituted cycloalkenyl claim 8 , substituted or unsubstituted cycloalkynyl claim 8 , substituted or unsubstituted aryl claim 8 , substituted or unsubstituted heteroaryl claim 8 , substituted or unsubstituted heteroalicyclyl claim 8 , ...

PROCESSES FOR PREPARING FLUOROKETOLIDES

Processes and intermediates for preparing fluoroketolide compounds are described herein. 2. The process of wherein the amine base is a cyclic claim 1 , a non-aromatic amine base claim 1 , or a base with a conjugate acid pKa of at least about 11 claim 1 , at least about 11.5 claim 1 , at least about 12 claim 1 , at least about 12.5 claim 1 , or at least about 13 claim 1 , or a combination of the foregoing.3. The process of wherein the base is sterically hindered.4. The process of wherein the base is a diamine.5. The process of wherein the base includes at least one nitrogen that does not have a hydrogen.6. The process of wherein the base includes at least one C=N group.7. The process of wherein the base is DBN or DBU claim 1 , or a combination thereof.8. The process of any one of to wherein the fluorinating agent is selected from the group consisting of NFSi claim 1 , Selectfluor claim 1 , and F-TEDA claim 1 , and combinations thereof.11. The process of wherein the compound of formula (I) is solithromycin or a salt thereof.17. A composition comprising solithromycin that is substantially free of or free of desfluoro solithromycin.18. A composition comprising solithromycin that is substantially free of or free of N-desmethyl solithromycin. This application claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application Ser. No. 62/129,305, filed Mar. 6, 2015, the disclosure of which is incorporated herein by reference.The invention described herein pertains to processes and intermediates for preparing fluoroketolide compounds.Fluoroketolide compounds have been reported to be highly effective in treating bacterial and protozoal infections. Moreover, fluoroketolide compounds have been reported to be particular effective in treating resistant bacterial and protozoal infections compared to corresponding non-fluoroketolides, macrolides, and azalides. However, reported manufacturing processes for ketolides proceed with low conversion, which leads to sometimes ...

Biopolymer synthesis system and method

The present invention provides improved automated systems and methods for synthesis of biopolymers including DNA and RNA. The automated systems and methods represent a number of improvements over existing systems for multiplex synthesis of biopolymers in a combinatorial fashion.

IMAGING AGENTS AND METHODS OF USE

An imaging agent and a method of its use for imaging a necrosis in a tissue of a subject. The imaging method may be positron emission tomography (PET). In at least one embodiment the imaging agent comprises 2-deoxy-2-[F]fluoroglucaric acid (F-FGA), or a pharmaceutically-acceptable salt thereof. The imaging agent may be disposed in a pharmaceutically-acceptable excipient, carrier, diluent, or vehicle. The imaging agent may be contained within a kit. The disclosure includes in at least one embodiment a method of preparing a radiopharmaceutical such as F-FGA for use in imaging. 1. An imaging agent comprising 2-deoxy-2-[F]fluoroglucaric acid , or a pharmaceutically-acceptable salt thereof.2. A composition comprising the imaging agent of disposed in a pharmaceutically-acceptable carrier claim 1 , diluent claim 1 , vehicle claim 1 , or excipient.3. A method of positron emission tomography (PET) imaging of a subject claim 1 , comprising:{'sup': 18', '18, 'administering to the subject an imaging agent comprising 2-deoxy-2-[F]fluoroglucaric acid (F-FGA), or a pharmaceutically-acceptable salt thereof;'}allowing the imaging agent to penetrate into a tissue of the subject, the tissue suspected to contain a necrosis; andcollecting a PET image of the tissue suspected to contain the necrosis.4. The method of claim 3 , comprising preparing the F-FGA claim 3 , or a pharmaceutically-acceptable salt thereof claim 3 , from a quantity of 2-deoxy-2-[F]fluoro-D-glucose (F-FDG) claim 3 , wherein the administering step occurs within about 3 hours after preparing the F-FGA.5. The method of claim 3 , wherein the subject is suspected of having tissue damage due to a cancer claim 3 , brain stroke claim 3 , traumatic brain injury claim 3 , or myocardial infarction.6. The method of claim 3 , wherein the tissue is selected from a group consisting of tissues of the myocardium claim 3 , brain claim 3 , breast claim 3 , prostate claim 3 , colon claim 3 , kidney claim 3 , spleen claim 3 , limb claim 3 ...

Process for galnac oligonucleotide conjugates

The invention comprises a process for the preparation of therapeutically valuable GalNAc cluster oligonucleotide conjugates. The process comprises the coupling of an alkali metal salt, earth alkali metal salt or a tetraalkylammonium salt of an oligonucleotide with a GalNAc cluster compound or with a salt thereof and a subsequent purification.

STEGANOGRAPHIC EMBEDDING OF INFORMATION IN CODING GENES

The present invention relates to the storage of information in nucleic acid sequences. The invention also relates to nucleic acid sequences containing desired information and to the design, production or use of sequences of this type. 126.-. (canceled)27. A method for producing an information containing nucleic acid molecule , the method comprising the steps:(a) selecting a starting nucleic acid molecule for the incorporation of the items of information;(b) selecting codons of the starting nucleic acid molecule that may be altered to incorporate the information;(c) altering the nucleotide sequence to incorporate the information, thereby generating the nucleotide sequence of the information containing nucleic acid molecule; and(d) producing the information containing nucleic acid molecule based upon the sequence generated in step (c);wherein the information containing nucleic acid molecule encodes a protein,wherein incorporation of the message does not change the amino acid sequence of the encoded protein,wherein the only codons altered to incorporate the information and read to disclose the information are codons for the following eight amino acids: arginine, valine, glycine, alanine, threonine, serine, leucine, and proline,wherein the encoded information is read from 5′ to 3′ and each codon encoding the eight amino acids is read as a zero or one,wherein a set of zeros and ones represents a character of information, andwherein expression level of the encoded protein in a human cell is not measurably decreased for the information containing nucleic acid molecule compared to the starting nucleic acid molecule.28. The method of claim 27 , wherein (i) the most prevalent codon in for each of the eight amino acids is read as a zero and the second most prevalent codon in for each of the eight amino acids is read as a one or (ii) the most prevalent codon in for each of the eight amino acids is read as the second most prevalent codon in for each of the eight amino acids is ...

Methods of inserting molecular barcodes

The present invention provides compositions, methods, and kits for inserting a plurality of synthetic transposons each comprising a different nucleic acid sequence (i.e., molecular barcode) in a target nucleic acid of interest to allow extraction of contiguity information in the target nucleic acid. The molecular barcodes are also useful for reducing amplification or sequencing bias and errors, and for guiding accurate sequence assembly of the target nucleic acid from sequencing reads. The compositions, methods, and kits described herein have many applications, including haplotyping, genome assembly, sequencing of repetitive regions, detection of structural variations and copy number variations, chromosomal conformation analysis, and methylation analysis.

Glycosylation Reactions Using Phenyl(trifluoroethyl)iodonium Salts

Provided are methods for the preparation of glycosylation products, including those represented by formula I: 2. The method of claim 1 , wherein Sugar is an optionally protected monosaccharide claim 1 , disaccharide claim 1 , or trisaccharide.3. The method of claim 1 , wherein Sugar is an optionally protected monosaccharide.4. The method of claim 1 , wherein Sugar is a protected glucopyranoside.5. The method of claim 1 , wherein R′ is selected from the group consisting of alkyl claim 1 , cycloalkyl claim 1 , alkenyl claim 1 , alkynyl claim 1 , aralkyl claim 1 , and heteroaralkyl; or R′—OH is a steroid or an optionally protected monosaccharide claim 1 , disaccharide claim 1 , trisaccharide claim 1 , or tetrasaccharide.6. The method of claim 1 , wherein R′—OH is cholesterol.7. The method of claim 1 , wherein R′—OH is a protected monosaccharide or disaccharide.8. The method of claim 1 , wherein the OH group of R′—OH that forms a bond to the anomeric carbon atom of Sugar is the C3 or C6 hydroxyl of a protected monosaccharide or disaccharide.10. The method of claim 1 , wherein Ris a phenyl or naphthyl group optionally substituted with one halo claim 1 , alkyl claim 1 , or haloalkyl.11. The method of claim 1 , wherein Ris an unsubstituted phenyl group.12. The method of claim 1 , wherein Rrepresents one or two substituents each independently selected from the group consisting of halo claim 1 , alkyl claim 1 , fluoroalkyl claim 1 , and perfluoroalkyl.13. The method of claim 1 , wherein Ris absent.14. The method of claim 1 , wherein Ris fluoroalkyl.15. The method of claim 1 , wherein Ris 2 claim 1 ,2 claim 1 ,2-trifluoroethyl.16. The method of claim 1 , wherein Xis selected from the group consisting of methanesulfonate claim 1 , trifluoromethanesulfonate claim 1 , benzenesulfonate claim 1 , p-toluenesulfonate claim 1 , bis(methanesulfonyl)amide claim 1 , bis(trifluoromethanesulfonyl)amide claim 1 , bis(benzenesulfonyl)amide claim 1 , (trifluoromethanesulfonyl)( ...

Nucleic Acid Amplification

Methods and compositions for the amplification of nucleic acids and generation of concatemers are disclosed. Amplification methods provided herein may be performed under isothermal conditions. Methods and compositions may include reagents such nucleic acid polymerases and primers. 14-. (canceled)5. A method for generating a concatemer comprising two or more copies of a double-stranded nucleic acid template , the method comprising , (i) a primary nucleic acid comprising the double-stranded nucleic acid template', '(ii) an isolated nucleic acid polymerase,', [ (1) the 5′ terminal nucleotide of the primer', '(2) an innermost nucleotide, wherein the innermost nucleotide is downstream', 'from the 5′ terminal nucleotide', '(3) a middle section between the 5′ terminal nucleotide and the innermost nucleotide, comprising one or more nucleotides, and, '(a) a tail region comprising'}, (1) the 3′ terminal nucleotide of the primer', '(2) an innermost nucleotide, wherein the innermost nucleotide is upstream from the 3′ terminal nucleotide', '(3) a middle section between the 3′ terminal nucleotide and the innermost nucleotide, comprising one or more nucleotides,, '(b) a template-binding region comprising'}], '(iii) a first primer comprising a 5′ terminal nucleotide, a 3′ terminal nucleotide, and two regions, 'wherein the template-binding region is complementary to a first strand of the nucleic acid template,', [ (1) the 5′ terminal nucleotide of the primer', '(2) an innermost nucleotide, wherein the innermost nucleotide is downstream', 'from the 5′ terminal nucleotide', '(3) a middle section between the 5′ terminal nucleotide and the innermost nucleotide, comprising one or more nucleotides, and, '(a) a tail region comprising'}, (1) the 3′ terminal nucleotide of the primer', '(2) an innermost nucleotide, wherein the innermost nucleotide is upstream from the 3′ terminal nucleotide', '(3) a middle section between the 3′ terminal nucleotide and the innermost nucleotide, comprising one ...

REVERSIBLE MODIFICATION OF NUCLEOTIDES

Disclosed herein, inter alia, are methods for modifying a nucleotide, for example including reacting a nucleotide having a 3′-O-oxime moiety such as 130.-. (canceled)32. The method of claim 31 , wherein R3 is CH.33. The method of claim 31 , wherein R4 is CH.34. The method of claim 31 , wherein Q is triphosphate.38. The method of claim 31 , wherein R2 has a molecular weight greater than 57 g/mol.39. The method of claim 38 , wherein R2 has a molecular weight greater than 100 g/mol.40. The method of claim 38 , wherein R2 has a molecular weight greater than 200 g/mol.41. The method of claim 31 , wherein R2 comprises a hydrocarbon ring.42. The method of claim 31 , wherein R2 comprises a heterocyclic ring.43. The method of claim 31 , wherein no more than 5% of the nucleotide is degraded.44. The method of claim 31 , wherein no more than 3% of the nucleotide is degraded.45. The method of claim 31 , wherein no more than 2% or no more than 1% of the nucleotide is degraded.46. The method of claim 31 , wherein no more than 3% of the nucleotide is degraded when the nucleotide comprises a cytosine nucleobase.47. The method of claim 31 , wherein the degradation of the nucleotide is less than half the degradation that would be obtained if R2 was a methyl group.48. The method of or claim 31 , wherein at least 95% of the nucleotide comprising a 3′-O-oxime moiety is consumed.49. The method of claim 31 , wherein at least 97% or at least 98% of the nucleotide comprising a 3′-O-oxime moiety is consumed.50. The method of claim 49 , wherein the method adds a blocking group in place of a 3′ protecting group to at least 98% of a population of nucleotides having a 3′ protecting group in no more than 3 hours. This application is a continuation of U.S. patent application Ser. No. 17/016,992, filed Sep. 10, 2020, which claims the benefit of U.S. Provisional Application No. 62/898,152, filed Sep. 10, 2019, which are incorporated herein by reference in their entireties and for all purposes.The ...

Deuterium-Stabilised Ribonucleic Acid (RNA) Molecules Displaying Increased Resistance to Thermal and Enzymatic Hydrolysis, Aqueous Compositions Comprising Stabilised RNA Molecules and Methods for Making Same

The invention relates to the field of RNA stabilisation, and more particularly to the use of deuterium oxide (DO) during storage and/or synthesis of RNA molecules. Described herein are deuterium-stabilised ribonucleic acid (RNA) molecules that display an increased resistance to thermal and enzymatic hydrolysis. Also described are aqueous compositions comprising stabilized RNA molecules and methods for making same. The invention is particularly useful for in the manufacture of RNA-based therapeutics, such as mRNA vaccines, to render them less sensitive to temperature fluctuations. 1. An aqueous composition comprising stabilised ribonucleic acid (RNA) molecules , said aqueous composition comprising at least one of: (i) RNA molecules and deuterium for stabilising the RNA molecules; and (ii) deuterium-stabilised RNA molecules that have been synthesised in the presence of deuterium.2. The aqueous composition of claim 1 , wherein said deuterium is present at a concentration of at least 85 atom % D.3. The aqueous composition of claim 1 , wherein said deuterium is present at a concentration of about 85 atom % D to about 99.9 atom % D.4. The aqueous composition of claim 1 , wherein said RNA molecules incorporates deuterium.5. The aqueous composition of claim 4 , wherein said RNA molecules comprise deuterated ribonucleoside tri-phosphates (rNTPs).6. The aqueous composition of claim 4 , wherein said RNA molecules comprise substitution of protium atoms by deuterium atoms.7. The aqueous composition of claim 4 , wherein said RNA molecules comprise a deuterium atom in the 2′OH-group on the ribose sugar moiety.8. The aqueous composition of claim 1 , wherein said stabilised RNA molecules display at least one of: i) increased structural integrity of their primary and/or secondary structure claim 1 , compared to non-stabilized RNA molecules; and ii) increased resistance to degradation compared to non-stabilised RNA molecules.9. The aqueous composition of claim 1 , wherein said ...

METHOD FOR PREPARING 2'-O-FUCOSYLLACTOSE

The present invention relates to a method for preparing 2′-O-fucosyllactose and to the protected fucosyl donor of the formula (I) used in this method. The method comprises reacting the fucose derivative of the formula (I) below with the compound of the general formula (II), in the presence of an activating reagent. In the formulae (I) and (II), the variables are each defined as follows: X is Br or a S-bound radical, namely —SCN, —S(O)—Ror —S—R, wherein Rpreferably is an optionally substituted phenyl, and Rpreferably is C-C-alkyl, 2-oxazolin-2-yl, 2-thiazolin-2-yl, benzoxazol-2-yl, benzothiazol-2-yl or pyridin-2-yl; Rare the same or different and are radicals of the formula SiRRR, wherein R, Rand Rpreferably are each methyl; Ris a C(=O)—Rradical or an SiRRRradical, wherein Ris preferably methyl, phenyl or tert-butyl, and R, Rand R14 preferably are each methyl; Rare the same or different and are C-C-alkyl or together form a linear C-C-alkanediyl, which is unsubstituted or has 1 to 6 methyl groups as substituents; Rare the same or different and are C-C-alkyl or together form a linear C-C-alkanediyl, which is unsubstituted or has 1 to 6 methyl groups as substituents. 123.-. (canceled)25. The method according to claim 24 , wherein X in formula (I) is{'br': None, 'sub': 'n', 'sup': X1', 'X2, '—SCN, —S(O)—Ror —S—R, where'} [{'sub': X1', '1', '4', '1', '4', '1', '4', '1', '4, 'Ris aryl which is unsubstituted or optionally has 1 to 5 substituents selected from halogen, C-C-alkyl, C-C-alkoxy, C-C-haloalkyl and C-C-haloalkoxy, and'}, {'sup': 'X2', 'sub': 1', '6', '1', '6', '1', '4', '1', '4', '1', '4', '1', '4, 'Ris selected from the group consisting of C-C-alkyl, C-C-haloalkyl, benzyl, wherein the phenyl moiety of benzyl is unsubstituted or optionally has 1 to 5 substituents selected from halogen, C-C-alkyl, C-C-alkoxy, C-C-haloalkyl and C-C-haloalkoxy, and 5- or 6-membered heterocyclyl, which bears a nitrogen atom in ortho position relative to the point of attachment and ...

MODULAR SYNTHESIS OF AMPHIPHILIC JANUS GLYCODENDRIMERS AND THEIR SELF-ASSEMBLY INTO GLYCODENDRIMERSOMES

The invention concerns compounds of the formula (I) wherein: Yand Yare independently a monosaccharide or disaccharide; Xand Xare independently —(R—O)—, —(R)—, —O—(R—O)—, —R—O—R—O— or a covalent bond; Qand Qare independently a nitrogen-containing heterocycle moiety; Zand Zare independently —(O—R)—, —(O—C(═O)—R)a-, —O—C(═O)—R—C(=0)-R—, —O—C(═O)—R—C(═O)—Ror a covalent bond; R-Rare each independently C-Calkyl; R-Rare each independently a linear or branched alkly group; b, c, d, e, f, and g are 0 or 1, provided b+c+d equals at least 2 and e+f+g equals at least 2; and a, m, p, and q are each an integer from 1-6. 2. The compound of claim 1 , wherein R-Rare each independently C-Clinear or branched alkyl group.3. The compound of claim 1 , wherein Yand Yare independently D-Mannose claim 1 , D-Galactose or D-Lactose.4. The compound of claim 1 , wherein Yand Yare the same.6. The compound of claim 1 , wherein a claim 1 , m claim 1 , p claim 1 , and q are each independently an integer from 1-4.7. The compound of claim 1 , wherein X claim 1 , X claim 1 , Zand Zare covalent bonds.8. The compound of claim 1 , wherein Xand Xare covalent bonds.9. The compound of claim 1 , wherein Zand Zare covalent bonds.11. The method of claim 10 , wherein Xand Xare covalent bonds.12. The method of claim 10 , wherein Zand Zare covalent bonds.13. The method of claim 10 , wherein X claim 10 , X claim 10 , Zand Zare covalent bonds.14. The method of claim 10 , wherein R-Rare each independently C-Clinear or branched alkyl group15. The method of claim 10 , wherein Yand Yare independently D-Mannose claim 10 , D-Galactose or D-Lactose.16. The method of claim 10 , wherein Yand Yare the same.18. The method of claim 10 , wherein R-Rare the same.19. A method of producing self-assembled amphiphilic Janus glycodendrimers comprising introducing a compound of into an aqueous media. This application claims benefit of U.S. Provisional Patent Application No. 61/825,698 filed May 21, 2013, the disclosure of which is ...

RNA CAPPING METHOD, PRODUCTION METHOD FOR MODIFIED RNA, AND MODIFIED RNA

An RNA capping method including a step of reacting a compound (1) represented by the following general formula (1) with an RNA in the presence of a Vaccinia virus capping enzyme (Rrepresents an oxo group, an alkoxy group, or a halogen atom; Ris either absent or represents an alkyl group; Rrepresents an amino group or a hydrogen atom; Ris either absent or represents a hydrogen atom or an alkyl group; Rrepresents a hydroxy group, an alkoxy group having 1 to 3 carbon atoms, an amino group, an azide group, —ORC≡CH, or —RR; Rrepresents a hydrogen atom, a hydroxy group, a halogen atom, an alkoxy group, an amino group, an azide group, —ORC≡CH, or —RR; and Arepresents an oxygen atom or a sulfur atom). 2. The RNA capping method according to claim 1 ,wherein the compound (1) is selected from the group consisting of N7-methylguanosine-5′-triphosphate, N1-methylguanosine-5′-triphosphate, O6-methylguanosine-5′-triphosphate, 6-chloroguanosine-5′-triphosphate, inosine-5′-triphosphate, 2′-deoxyguanosine-5′-triphosphate, araguanosine-5′-triphosphate, 2′-fluoro-2′-deoxyguanosine-5′-triphosphate, 2′-O-methylguanosine-5′-triphosphate, 3′-O-methylguanosine-5′-triphosphate, 2′-amino-2′-deoxyguanosine-5′-triphosphate, 3′-amino-2′,3′-dideoxyguanosine-5′-triphosphate, 2′-azido-2′-deoxyguanosine-5′-triphosphate, 3′-azido-2′,3′-dideoxyguanosine-5′-triphosphate, 3′-(O-propargyl)-guanosine-5′-triphosphate, 2′/3′-O-(2-aminoethyl-carbamoyl)-guanosine-5′-triphosphate and guanosine-5′-O-(1-thiotriphosphate).4. The method for producing a modified RNA according to claim 3 ,{'sub': '1', 'wherein the compound (1) is selected from the group consisting of N7-methylguanosine-5′-triphosphate, N-methylguanosine-5′-triphosphate, O6-methylguanosine-5′-triphosphate, 6-chloroguanosine-5′-triphosphate, inosine-5′-triphosphate, 2′-deoxyguanosine-5′-triphosphate, araguanosine-5′-triphosphate, 2′-fluoro-2′-deoxyguanosine-5′-triphosphate, 2′-O-methylguanosine-5′-triphosphate, 3′-O-methylguanosine-5′-triphosphate, 2 ...

OLIGONUCLEOTIDE SYNTHESIS METHOD USING HIGHLY DISPERSIBLE LIQUID-PHASE SUPPORT

A nucleic acid synthesis method enabling a reaction in a fluid (flow) with a highly dispersible liquid-phase support to improve coupling efficiency is provided. 2. The method for synthesizing an oligonucleotide according to claim 1 , wherein a dissolution solution of the hydrophobic group-bonded nucleoside or hydrophobic group-bonded oligonucleotide and the nucleoside phosphoramidite compound in a non-polar solvent and a dissolution solution of the acid/azole complex compound in a non-polar solvent are separately prepared claim 1 , and are mixed.3. The method for synthesizing an oligonucleotide according to claim 1 , wherein a dissolution solution of the hydrophobic group-bonded nucleoside or hydrophobic group-bonded oligonucleotide and the nucleoside phosphoramidite compound in a non-polar solvent and a dissolution solution of the acid/azole complex compound in a non-polar solvent are separately fed into a flow path to continuously conduct the condensation reaction in the flow path.5. The method for synthesizing an oligonucleotide according to claim 4 , wherein in Formula (3) claim 4 , R is an octadecyl group. The present invention relates to an oligonucleotide synthesis method enabling a flow reaction with a highly dispersible liquid-phase support.A nucleic acid synthesis method at present mainly employs a solid-phase synthesis method according to a phosphoramidite method (Non Patent Literatures 1 to 3). In the phosphoramidite method, a 5′-hydroxyl group, an amino group of a base, and an amidite monomer having a protected 2′-hydroxyl group, if in RNA, are coupled with a promoter (activator) such as tetrazole compounds and imidazole compounds, and the resulting product is oxidized to form a phosphodiester bond (see the following formula):where the protecting group represents DMTr, MMTr or the like; the protected base represents Bz-adenine, Bz-cytosine, iBu-guanine, thymine, uracil, Pac-adenine, Ac-cytosine, iPr-Pac-guanine, dmf-guanine, another protected modified ...

CYTIDINE DERIVATIVE DIMERS AND APPLICATIONS THEREOF

The present disclosure provides cytidine derivative dimers, salts and compositions of the cytidine derivative dimers, and methods of making and using the cytidine derivative dimers that are useful for treating a neoplasm in mammalian subjects. A cytidine derivative dimer may have the following general formula (I): 2. The tumor inhibiting drug according to claim 1 , wherein R3 is hydrogen and R4 is hydrogen.3. The tumor inhibiting drug according to claim 2 , wherein R1 and R2 are same.4. The tumor inhibiting drug according to claim 1 , wherein the tumor inhibiting drug is capable of treating a blood cancer or a malignant solid tumor.5. The tumor inhibiting drug according to claim 1 , wherein the tumor inhibiting drug is capable of treating a colon cancer.7. The method according to claim 6 , further comprising:mixing and adding the compound having the general formula (IV), the compound having the general formula (III), and N,N′-dicyclohexylcarbodiimide (DCC) to methylene chloride,adding in 4-dimethylaminopyridine (DMAP) for a reaction, andwhen the reaction is measured to be completed, washing, drying, and concentrating the reaction mixture to form a dried solid under a reduced pressure,wherein trifluoroacetic acid (TFA) and dichloromethane (DCM) are added to the dried solid, stirred at room temperature, cooled in an ice bath, and filtered to provide a white solid, and wherein the white solid is concentrated into a viscous oil, purified by column chromatography to produce the cytidine derivative dimer. This application is a continuation application of U.S. patent application Ser. No. 14/624,513, filed on Feb. 17, 2015. U.S. patent application Ser. No. 14/624,513 claims the priority of Chinese Patent Application No. 201410652724.4, entitled “Cytidine Derivative Dimer and Applications thereof”, filed on Nov. 17, 2014, the entire content of which is incorporated herein by reference.The present disclosure relates to the field of antitumor compounds and, more particularly, ...

CHLORINATION OF CARBOHYDRATES AND CARBOHYDRATE DERIVATIVES

Disclosed is a method for chlorinating a carbohydrate or a derivative thereof to produce a polychlorinated carbohydrate or a derivative thereof, such as sucralose, the method involves (i) reacting the carbohydrate or derivative thereof with a chlorinating agent to obtain a reaction mixture comprising said polychlorinated carbohydrate or derivative thereof and at least one under-chlorinated carbohydrate or derivative thereof, (ii) returning the at least one under-chlorinated carbohydrate or derivative thereof to a chlorinating step and further chlorinating the at least one under-chlorinated carbohydrate or derivative thereof to obtain the desired polychlorinated carbohydrate or derivative thereof; and (iii) optionally repeating steps (i) and (ii) “n” times where n≧1. The polychlorinated carbohydrate or a derivative thereof is obtained in high yields. 1. A method for chlorinating a carbohydrate or a derivative thereof , wherein said carbohydrate or derivative thereof has two or more hydroxyl groups , to produce a polychlorinated carbohydrate or a derivative thereof , said polychlorinated carbohydrate or a derivative thereof having a desired number of chlorine atoms replacing two or more of the hydroxyl groups at desired locations in its molecular structure , the method comprising:(i) reacting the carbohydrate or derivative thereof with a chlorinating agent to obtain a reaction mixture comprising said polychlorinated carbohydrate or derivative thereof and at least one under-chlorinated carbohydrate or derivative thereof;(ii) returning the at least one under-chlorinated carbohydrate or derivative thereof to a chlorinating step and further chlorinating the at least one under-chlorinated carbohydrate or derivative thereof to obtain the desired polychlorinated carbohydrate or derivative thereof; and(iii) optionally repeating steps (i) and (ii) “n” times where n≧1.2. The method of claim 1 , further comprising:(iv) quenching at least a portion of the reaction mixture from ...

Process and apparatus for sequential synthesis of biological polymers

A method and apparatus for nucleic acid synthesis. The method employs a device including at least one deprotection unit to carry out a step of deprotection, at least one coupling unit to carry out a step of coupling, at least one oxidation/thiolation unit to carry out a step of oxidation orthiolation, at least one capping unit to carry out a step of capping, and at least one washing unit to carry out a step of washing. A plurality of reaction vessels for nucleic acid synthesis are moved to the units in accord with a synthesis scheme for a desired nucleic acid sequence and at least two reaction vessels are simultaneously acted upon at several of the units in series.

METHOD FOR THE SYNTHESIS OF PHOSPHORUS ATOM MODIFIED NUCLEIC ACIDS

Described herein are methods of syntheses of phosphorous atom-modified nucleic acids comprising chiral X-phosphonate moieties. The methods described herein provide backbone-modified nucleic acids in high diasteteomeric purity via an asymmetric reaction of an achiral molecule comprising a chemically stable H-phophonate moiety with a nucleoside/nucleotide. 1. A method for a synthesis of a nucleic acid comprising a chiral X-phosphonate moiety comprising:reacting a molecule comprising an achiral H-phosphonate moiety, a chiral reagent, and a nucleoside comprising a 5′-OH moiety to form a condensed intermediate; andconverting the condensed intermediate to the nucleic acid comprising a chiral X-phosphonate moiety, wherein the nucleic acid comprises a modified sugar.2. The method of claim 1 , wherein the modified sugar contains one or more substituents at the 2′-position.3. The method of claim 2 , wherein a substituent at the 2′-position is selected from the group consisting of: F claim 2 , CF claim 2 , CN claim 2 , N claim 2 , NO claim 2 , NO claim 2 , O- claim 2 , S- claim 2 , or N-alkyl; O- claim 2 , S- claim 2 , or N-alkenyl; O- claim 2 , S- claim 2 , or N-alkynyl; or O-alkyl-O-alkyl claim 2 , O-alkyl-N-alkyl or N-alkyl-O-alkyl wherein the alkyl claim 2 , alkenyl and alkynyl may be substituted or unsubstituted C-Calkyl or C-Calkenyl and alkynyl.4. The method of claim 2 , wherein a substituent is —O(CH)OCH claim 2 , wherein n is from 1 to about 10.5. The method of claim 4 , wherein n is 1.6. The method of claim 2 , wherein a substituent is MOE.7. The method of claim 2 , wherein a substituent is F.8. The method of claim 2 , wherein a substituent is O-alkyl claim 2 , wherein alkyl is substituted or unsubstituted C-Calkyl.9. The method of claim 2 , wherein a substituent is O-alkyl-O-alkyl claim 2 , wherein alkyl is substituted or unsubstituted C-Calkyl.10. The method of claim 2 , wherein the nucleic acid comprises one or more natural sugar of DNA or RNA.11. The method of ...

METHOD TO PRODUCE WATER-SOLUBLE SUGARS FROM BIOMASS USING SOLVENTS CONTAINING LACTONES

A process to produce an aqueous solution of carbohydrates that contains C6-sugar-containing oligomers, C6 sugar monomers, C5-sugar-containing oligomers, C5 sugar monomers, or any combination thereof is presented. The process includes the steps of reacting biomass or a biomass-derived reactant with a solvent system including a lactone and water, and an acid catalyst. The reaction yields a product mixture containing water-soluble C6-sugar-containing oligomers, C6-sugar monomers, C5-sugar-containing oligomers, C5-sugar monomers, or any combination thereof. A solute is added to the product mixture to cause partitioning of the product mixture into an aqueous layer containing the carbohydrates and a substantially immiscible organic layer containing the lactone. 1. A process to produce an aqueous solution of carbohydrates comprising C6-sugar-containing oligomers , C6-sugar monomers , C5-sugar-containing oligomers , C5-sugar monomers , or any combination thereof , the process comprising:(a) reacting biomass or a biomass-derived reactant with a solvent system comprising (i) an organic solvent selected from the group consisting of beta-, gamma-, and delta-lactones, and combinations thereof, and (ii) at least about 1 wt % water; in the presence of an acid catalyst for a time and under conditions to yield a product mixture wherein at least a portion of water-insoluble C6-sugar-containing polymers or oligomers, or water-insoluble C5-sugar-containing polymers or oligomers, if present in the biomass or biomass-derived reactant, are converted to water-soluble C6-sugar-containing oligomers, C6-sugar monomers, C5-sugar-containing oligomers, C5-sugar monomers, or any combination thereof; and then(b) adding a solute to the product mixture of step (a) in an amount sufficient to cause partitioning of the product mixture into an aqueous layer and a substantially immiscible organic layer.2. The method of claim 1 , wherein the organic solvent is miscible with water.3. The method of claim 1 ...

METHODS FOR REMOVING TRIAZINE FROM N-METHYLIMIDAZOLE FOR SYNTHESIS OF OLIGONUCLEOTIDE

Methods for removing 1,3,5-trimethylhexahydro-1,3,5-triazine and N-methylenemethanamine from a N-methylimidazole and methods for making oligonucleotides using N-methylimidazole are provided. In one embodiment, a method for removing 1,3,5-trimethylhexahydro-1,3,5-triazine and N-methylenemethanamine from a feedstock containing N-methylimidazole includes contacting the feedstock with small or medium pore molecular sieves. The small or medium pore molecular sieves adsorb 1,3,5-trimethylhexahydro-1,3,5-triazine and N-methylenemethanamine from the feedstock. The method further includes separating the small or medium pore molecular sieves from the feedstock. 1. A method for removing 1 ,3 ,5-trimethylhexahydro-1 ,3 ,5-triazine and N-methylenemethanamine from a feedstock containing N-methylimidazole , the method comprising:contacting the feedstock with small or medium pore molecular sieves, wherein the small or medium pore molecular sieves adsorb 1,3,5-trimethylhexahydro-1,3,5-triazine and N-methylenemethanamine from the feedstock; andseparating the small or medium pore molecular sieves from the feedstock.2. The method of wherein contacting the feedstock with small or medium pore molecular sieves comprises contacting the feedstock with synthetic molecular sieves having a pore aperture size of no more than about 0.6 nm.3. The method of wherein contacting the feedstock with small or medium pore molecular sieves comprises contacting the feedstock with silicoaluminophosphate (SAPO) molecular sieves.4. The method of wherein contacting the feedstock with small or medium pore molecular sieves comprises contacting the feedstock with SAPO-34 molecular sieves.5. The method of wherein contacting the feedstock with small or medium pore molecular sieves comprises:mixing the feedstock with the small or medium pore molecular sieves in a chamber,heating the chamber to form a reflux of condensed vapor, andreturning the reflux to the chamber.6. The method of further comprising the step of ...

METHOD FOR PREPARING ANALYTICAL SAMPLE, ANALYSIS METHOD, AND KIT FOR PREPARING ANALYTICAL SAMPLE

A method for preparing an analytical sample for analysis of a glycan contained in a sample includes: performing an amidation reaction that amidates a lactone structure included in the glycan through contacting the sample with a reaction solution that is basic; adding an acidic solution to the reaction solution after the reaction solution is subjected to the amidation reaction; and purifying the sample contained in the reaction solution after the acidic solution is added to the reaction solution by using a carrier for hydrophilic interaction chromatography. 1. A method for preparing an analytical sample for analysis of a glycan contained in a sample , the method comprising:performing an amidation reaction that amidates a lactone structure included in the glycan through contacting the sample with a reaction solution that is basic;adding an acidic solution to the reaction solution after the amidation reaction; andpurifying the sample contained in the reaction solution by using a carrier for hydrophilic interaction chromatography after the acidic solution is added to the reaction solution.2. The method for preparing an analytical sample according to claim 1 , whereinpH of the reaction solution after the acidic solution is added to the reaction solution is 10 or lower.3. The method for preparing an analytical sample according to claim 1 , the method further comprising:performing a lactonization reaction that lactonizes at least a part of sialic acids included in the glycans before the amidation reaction.4. The method for preparing an analytical sample according to claim 2 , the method further comprising:performing a lactonization reaction that lactonizes at least a part of sialic acids included in the glycans before the amidation reaction.5. The method for preparing an analytical sample according to claim 3 , whereinthe lactonization reaction is performed through contacting the sample with a lactonization reaction solution containing a dehydration condensation agent.6. ...

Polyols, preparation and use thereof

The present invention relates to polyols and the preparation and use thereof.

OLIGONUCLEOTIDES CONTAINING HIGH CONCENTRATIONS OF GUANINE MONOMERS

This invention pertains to methods for oligonucleotide synthesis, specifically the synthesis of oligonucleotides that contain a high content of guanine monomers. In more detail, the invention relates to a method for coupling a nucleoside phosphoramidite during the synthesis of an oligonucleotide to a universal support, to a first nucleoside, or to an extending oligonucleotide. The invention further relates to oligonucleotides obtainable by the methods of the invention. 1. A method for coupling a nucleoside phosphoramidite during the synthesis of an oligonucleotide to a universal support , to a first nucleoside , or to an extending oligonucleotide , said method comprising the step of: (a) at least one first solvent, wherein said at least one first solvent is a polar aprotic solvent, and wherein said at least one first solvent is not acetonitrile;', '(b) an activating reagent; and', '(c) said nucleoside phosphoramidite;, '(i) generating a coupling solution, wherein said coupling solution compriseswherein the concentration of said nucleoside phosphoramidite in said coupling solution is at least 0.03 M; and(ii) contacting said coupling solution with said universal support, with said first nucleoside, or with said extending oligonucleotide.2. The method of claim 1 , wherein said at least one first solvent is selected from the group consisting of:(a) sulfolane;(b) 1-methylpyrrolidin-2-one;(c) N,N-dimethylacetamide;(d) tetramethylurea; and(e) dimethylsulfoxide (DMSO).3. (canceled)4. The method of claim 1 , wherein the concentration of said nucleoside phosphoramidite in said coupling solution is 0.03 to 0.30 M.57-. (canceled)86. The method of any one of claim claim 1 , wherein the ratio (v/v) of said at least one first solvent to said second solvent is between 5:1 and 1:2.96. The method of any one of claim claim 1 , wherein the ratio (v/v) of said at least one first solvent to said second solvent is 1:1.10. The method of claim 1 , wherein said first nucleoside and/or said ...

SACCHARIDE STRUCTURES AND METHODS OF MAKING AND USING SUCH STRUCTURES

Described are oligosaccharides having a protecting group at two, a plurality, a majority of, or each position in the oligosaccharide which is amenable to derivatization. Collections, libraries and methods of making and using such oligosaccharides are also described. 124-. (canceled)26. The method of claim 25 , wherein the protected oligosaccharide is treated to produce the oligosaccharide having a preselected pattern of sulfation and/or acetylation.27. The method of claim 25 , wherein the protected oligosaccharide is treated such that at least one disaccharide unit of the oligosaccharide with a preselected pattern of derivatization is acetylated at position R.28. The method of claim 25 , wherein the protected oligosaccharide is treated such that at least one disaccharide unit of the oligosaccharide with a preselected pattern of derivatization is sulfated or acetylated at least one of positions R claim 25 , R claim 25 , R claim 25 , R claim 25 , or R.29. The method of claim 25 , further comprising treating the protected oligosaccharide with an agent which replaces one or more of the protecting groups that does not allow for derivatization with a sulfation or acetyl group.30. The method of claim 25 , wherein the protected oligosaccharide is treated such that at least one disaccharide unit of the oligosaccharide with a preselected pattern of derivatization has an OSOH group at position OR; an OH group at position OR; and an NHSOH group at position R.31. The method of claim 25 , wherein the protected oligosaccharide is treated such that at least one disaccharide unit of the oligosaccharide with a preselected pattern of derivatization has an OH group at position OR; an OSOH group at position OR; and a NHAc group at position R.32. The method of claim 25 , wherein the protected oligosaccharide is treated such that at least one disaccharide unit of the oligosaccharide with a preselected pattern of derivatization has an OSOH group at position OR; an OH group at position OR; ...

STEGANOGRAPHIC EMBEDDING OF INFORMATION IN CODING GENES

The present invention relates to the storage of items of information in nucleic acid sequences. The invention also relates to nucleic acid sequences in which desired items of information are contained, and to the design, production or use of such sequences. 1. A method for designing nucleic acid sequences in which items of information are contained , which comprises the steps: assigning a second specific value to at least one second nucleic acid codon from the group,', 'optionally assigning one or more further values to in each case at least one further nucleic acid codon from the group,', 'in which the first and second and optionally further values are in each case allocated at least once within the group of codons which encode the same amino acid;, '(a) assigning a first specific value to at least one first nucleic acid codon from a group of degenerate nucleic acid codons which encode the same amino acid,'}(b) providing an item of information to be stored as a series of n values which are in each case selected from first and second and optionally further values;(c) providing a starting nucleic acid sequence, wherein the sequence comprises n degenerate codons to which first and second and optionally further values are assigned according to (a), in which n is an integer ≧1; and(d) designing a modified sequence of the nucleic acid sequence from (c), in which, at the positions of the n degenerate codons of the starting nucleic acid sequence, in each case one nucleic acid codon is selected from the group of degenerate codons which encode the same amino acid, to which codon there corresponds a value due to the assignment from (a) so that the series of the values assigned to the n codons results in the item of information to be stored.2. The method according to claim 1 , in which the amino acids in step (a) are selected from six-fold encoded amino acids claim 1 , such as leucine claim 1 , serine claim 1 , arginine claim 1 , and/or four-fold encoded amino acids claim 1 , ...

USE OF CO2 FOR THE SYNTHESIS OF CYCLIC GLYCOCARBONATES AND LINEAR POLYGLYCOCARBONATES BY POLYCONDENSATION FROM GLYCANS

Provided herein are methods for synthesizing cyclic carbonates, glycocarbonates, and polyglycocarbonates by reacting polyol glycans with carbon dioxide. Synthesis can include selective polycondensation of polyol glycan hydroxyl moieties. 1. A method for making glycocarbonates , the method comprising reacting a polyol glycan with carbon dioxide , wherein the glycan comprises a closed chain structure.2. The method of claim 1 , wherein the polyol glycan comprises hexose.3. The method of claim 1 , wherein the polyol glycan comprises a pyranose moiety.4. The method of claim 1 , wherein the polyol glycan comprises a pyranoside.5. The method of claim 1 , wherein the polyol glycan comprises a polysaccharide moiety.6. The method of claim 1 , wherein the polyol glycan comprises a glycan derivative.7. The method of claim 1 , wherein reaction occurs in the presence of one or more solvents.8. The method of claim 7 , wherein the solvents are one or more of dibromomethane claim 7 , dimethylformamide claim 7 , and an ionic liquid.9. The method of claim 8 , wherein the ionic liquid comprises 1-Butyl-3-methylimidazolium hexafluorophosphate.10. The method of claim 1 , further comprising selectively protecting one or more hydroxyl moieties of the polyol glycan before reacting claim 1 , wherein the polyol glycan comprises at least three hydroxyl moieties.11. The method of claim 10 , wherein protecting comprises methylating.12. The method of claim 1 , wherein reacting is conducted in the presence of a catalyst.13. The method of claim 12 , wherein the catalyst comprises 1 claim 12 ,8-diazabicyclo [5.4.0] undec-7-ene.14. The method of claim 1 , wherein the method is free of phosgene claim 1 , phosgene derivatives claim 1 , and isocyanates.15. The method of claim 1 , wherein reacting is conducted at a pressure between about 1 bar and about 20 bar.16. The method of claim 1 , wherein reacting is conducted at a temperature of between about 60° F. and 80° F.17. The method of claim 1 , wherein ...

Methods of Synthesizing and Labeling Nucleic Acid Molecules

The present invention is generally related to composition, kits and methods for synthesizing nucleic acid molecules and particularly for synthesizing labeled nucleic acid molecules. Specifically, the invention relates to methods, kits and compositions for synthesizing indirectly labeled nucleic acid molecules. The labeled nucleic acid molecules produced in accordance with the invention are particularly suited as labeled probes for nucleic acid detection, diagnostics, and array analysis. 143-. (canceled)44. A method of synthesizing one or more nucleic acid molecules comprising incubating one or more nucleic acid templates with 2 or more modified nucleotides under conditions sufficient to make one or more first nucleic acid molecules complementary to all or a portion of said one or more templates , wherein at least one said nucleic acid molecule contains said 2 or more modified nucleotides incorporated therein.45. A method of claim 44 , wherein at least one of said modified nucleotides is selected from the group consisting of aminoallyl-dUTP and aminohexyl-dATP.46. A method of claim 44 , wherein at least two of said modified nucleotides is selected from the group consisting of aminoallyl-dUTP and aminohexyl-dATP.47. A method of claim 44 , wherein said nucleic acid template is mRNA or a population of mRNA molecules.48. A method of claim 44 , further comprising incubating said one or more nucleic acid molecules under conditions sufficient to make one or more second nucleic acid molecules complementary to all or a portion of said one or more first nucleic acid molecules.49. A method of claim 44 , further comprising incubating said one or more nucleic acid molecules in the presence of one or more detectable labels under conditions sufficient to couple one or more of said labels to at least one of said modified nucleotides incorporated therein.50. A method of claim 49 , wherein at least one of said labels is a fluorescent label.51. A method of claim 49 , wherein at least ...

Method for the Isomerisation of Glucose into Fructose

The invention relates to a method for the isomerisation of glucose into fructose in water in the presence of a solid base catalyst characterised by its reversibility of COadsorption at a low temperature, the catalyst being a catalyst comprising at least one supported or non-supported lanthanide oxide or a molecular sieve based on silicon containing the organic template thereof. The invention also relates to a method for preparing HMF from glucose, comprising the isomerisation of glucose into fructose. 1. A method for isomerisation of glucose into fructose in water in the presence of a solid basic catalyst , characterized by the reversibility of the COadsorption isotherms at low temperature , notably at 30° C. and preferably a differential COadsorption heat , measured at 30° C. , comprised between 60 and 110 kJ·mol , preferably between 75 and 90 kJ·mol , the catalyst being a catalyst comprising at least one scandium oxide or one lanthanide oxide selected from the chemical elements with atomic number from 57 to 71 , either supported or not supported or a molecular sieve based on silicon containing its organic template.2. (canceled)3. The method according to claim 1 , for which the catalyst is selected from lanthanide oxides claim 1 , either supported or not claim 1 , optionally hydroxylated and/or carbonated claim 1 , mixed oxides of lanthanides with other metals claim 1 , either supported or not claim 1 , optionally hydroxylated and/or carbonated claim 1 , or molecular sieves based on silicon containing their organic template.4. The method according to claim 1 , for which the catalyst is selected from mixed oxides of lanthanides with other alkaline or earth alkaline metals or supported oxides of lanthanides claim 1 , the supports being carbonaceous supports or metal oxides.5. The method according to claim 1 , for which the catalyst is MgLaO or LaO supported on coal.6. The method according to claim 1 , for which the catalyst is a molecular sieve of the M41S claim 1 , ...

Chemoenzymatic Synthesis of Trehalose Analogs

The present invention provides methods of synthesizing trehalose analogues; methods of detecting mycobacteria, and trehalose analogues. 1. A method for synthesizing trehalose analogues comprising contacting a glucose analogue with a trehalose synthase , a magnesium salt and a monosaccharide donor , with the provisio that either the glucose analogue is not glucose or the monosachharide donor is not a glucose donor.2. The method according to claim 1 , wherein a single trehalose synthase is used.5. The method according to claim 1 , wherein the monosaccharide donor is selected from the group consisting of a nucleotide diphosphate glucose and glucosyl fluoride.6. The method of claim 5 , wherein the nucleotide diphosphate glucose is UDP-glucose.7. The method of claim 1 , wherein the trehalose synthase is thermostable.8. The method of claim 1 , wherein the trehalose synthase is unidirectional.9Thermoproteus tenax.. The method of claim 1 , wherein the trehalose synthase is from10. The method of claim 1 , further comprising contacting the glucose analogue with a buffer.11. A method of detecting live mycobacteria in a sample comprising:a. contacting a glucose analogue with a trehalose synthase, a magnesium salt and a monosaccaride donor to form a trehalose analogue;b. contacting a sample with the trehalose analogue;c. detecting the labeled mycobacteria;wherein the trehalose analogue is labeled with a detectable moiety.12. The method of claim 11 , wherein the sample is sputum claim 11 , cerebrospinal fluid claim 11 , pericardial fluid claim 11 , synovial fluid claim 11 , ascitic fluid claim 11 , blood claim 11 , bone marrow claim 11 , urine claim 11 , or feces.13. The method of claim 11 , wherein the sample is contacted with the reaction mixture formed in step (a).14. The method according to claim 11 , wherein the detectable moiety is H claim 11 , C claim 11 , F or N.17. The method according to claim 11 , wherein the glucose donor is selected from the group consisting of a ...

SYNTHESIS OF R-GLUCOSIDES, SUGAR ALCOHOLS, REDUCED SUGAR ALCOHOLS, AND FURAN DERIVATIVES OF REDUCED SUGAR ALCOHOLS

Disclosed herein are methods for synthesizing 1,2,5,6-hexanetetrol (HTO), 1,6 hexanediol (HDO) and other reduced polyols from C5 and C6 sugar alcohols or R glycosides. The methods include contacting the sugar alcohol or R-glycoside with a copper catalyst, most desirably a Raney copper catalyst with hydrogen for a time, temperature and pressure sufficient to form reduced polyols having 2 to 3 fewer hydoxy groups than the starting material. When the starting compound is a C6 sugar alcohol such as sorbitol or R-glycoside of a C6 sugar such as methyl glucoside, the predominant product is HTO. The same catalyst can be used to further reduce the HTO to HDO. 1. A method of synthesizing R-glycosides comprising:{'sub': 1', '4, 'heating an acetyl cellulose pulp in the presence of an alcohol of the formula ROH, where R is a C-Calkyl group, and an acid catalyst selected from the group consisting of phosphoric acid and a sulfonic acid, for a time and at a temperature sufficient to form an R-glycoside fraction from the acetyl cellulose pulp.'}2. The method of claim 1 , wherein the acetyl cellulose pulp is derived from a monocot species.3. The method of claim 2 , wherein the monocot species is selected from the group consisting of grasses claim 2 , corn stover claim 2 , bamboo claim 2 , wheat straw claim 2 , barley straw claim 2 , millet straw claim 2 , sorghum straw claim 2 , and rice straw.4. The method of claim 1 , wherein the alcohol and the acetyl cellulose pulp are present in a weight ratio of at least 5:1 alcohol to acetyl cellulose pulp.5. The method of claim 1 , wherein the acid catalyst is a sulfonic acid of the formula RSOH where R is an alkyl or cycloalkyl group.6. The method of claim 1 , wherein the acid catalyst is present in a weight percent relative to the weight of the alcohol of at least 0.5%.7. The method of claim 1 , wherein the acetyl cellulose pulp is heated to a temperature between 170° C. and 200° C.8. A method of synthesizing sugar alcohols comprising:{' ...

METHOD FOR THE PREPARATION OF 2-(4-METHOXYCARBONYLPYRAZOL-1-YL)ADENOSINE AND 2-(4-ETHOXYCARBONYLPYRAZOL-1-YL)ADENOSINE

A method for the preparation of 2-(4-methoxycarbonylpyrazol-1-yl)adenosine of formula 1a and 2-(4-ethoxycarbonylpyrazol-1-yl)adenosine of formula 1b by reaction of 2-hydrazinoadenosine of formula III and the sodium salt of 3,3-dimethoxy-2-methoxycarbonylpropen-1-ol of formula Va or the sodium salt of 3,3-diethoxy-2-ethoxycarbonylpropen-1-ol of formula Vb in combination with a solvent and an acidic agent. 2. The method according to claim 1 , wherein the acidic agent is formic claim 1 , acetic or propionic acid.3. The method according to claim 1 , wherein the acidic agent is hydrochloric claim 1 , sulphuric or phosphoric acid.4. The method according to claim 1 , wherein the acidic agent is disulphites claim 1 , hydrogen sulphates or dihydrogen phosphates.5. The method according to claim 1 , wherein the solvent is water or a solvent from the group of alcohols or a solvent from the group of polar aprotic solvents or their mutual mixtures.6. The method according to claim 1 , wherein the reaction is carried out for 2 to 7 hours.7. The method according to claim 1 , wherein the reaction is carried out at the temperatures of 25 to 60° C.8. 2-(4-Methoxycarbonylpyrazol-1-yl)adenosine of formula Ia claim 1 , characterized by:Melting point—uncorrected: 225-228° C.The Differential Scanning calorimetry DSC exhibits an endothermic transition at 227.6° C.{'sup': '1', 'sub': '6', 'H NMR (DMSO-d, 400 MHz) δ 8.94 (1H, d, J=0.7 Hz), 8.41 (1H, s), 8.11 (1H, d, J=0.7 Hz), 7.83 (2H, s), 5.92 (1H, d, J=6, 2 Hz), 5.49 (1H, d, J=6.5 Hz), 5.21 (1H, d, J=4.8 Hz), 5.00 (1H, t, J=5.7 Hz), 4.59 (1H, m), 4.16 (1H, m), 3.95 (1H, m), 3.79 (3H, s), 3.63 (2H, m)'}{'sup': '13', 'sub': '6', 'C NMR (DMSO-d, 100 MHz) δ 162.85, 156.87, 150.56, 150.52, 142.54, 140.71, 132.51, 118.60, 115.91, 87.66, 86.13, 74.11, 70.87, 61.87, 51.99.'} The invention relates to a new method for the preparation of 2-(4-methoxycarbonylpyrazol-1-yl)adenosine of formula Ia and 2-(4-ethoxycarbonylpyrazol-1-yl)adenosine of formula ...