СУЛЬФОНАМИДНЫЕ ИНГИБИТОРЫ HIY - АСПАРТИЛ-ПРОТЕАЗЫ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СПОСОБ ЛЕЧЕНИЯ, СПОСОБ ИДЕНТИФИКАЦИИ ИНГИБИТОРА

Изобретение относится к новому классу сульфонамидов, которые являются ингибиторами аспартил-протеазы формулы I. Изобретение относится к новому классу H1У аспартил-протеазных ингибиторов, отличающемуся специфическими структурными и физико-химическими характеристиками. Изобретение относится также к фармацевтическим композициям, содержащим эти соединения. Соединения и фармацевтические композиции изобретения особенно подходят для ингибирования Н1У-1 и Н1У-2 протеазной активности, и, соответственно, их можно с выгодой использовать в качестве вирусных агентов против Н1У-1 и Н1У-2 вирусов. Изобретение относится также к способам ингибирования активности Н1У аспартил-протеазы, за счет использования соединений настоящего изобретения, и способам скринирования соединений по их анти-HIУ активности. 5 с. и 21 з.п. ф-лы, 3 ил., 8 табл.

АРИДЗАМЕЩЕННЫЕ ПИПЕРАЗИНОВЫЕ ПРОИЗВОДНЫЕ

... 1. Соединение формулы или его фармацевтически приемлемая соль, где V отсутствует или представляет собой -(С=O)-; W представляет собой N, СН или С-ОН; Y1, Y3, Y4, и Y5 независимо представляют собой CR1 или азот; Z представляет собой азот или CR2; каждый R1 независимо представляет собой (i) водород, галоген, гидрокси, нитро, циано, амино, аминокарбонил, C1-С6алкил, С2-С6алкенил, С3-С6алкинил, C1-С6алкокси, галогенС1-С6алкил, галогенС1-С6алкокси, гидроксиС1-С6алкил, (С1-С4алкокси)С1-С4алкил, C1-С6алкилтио, аминоС1-С6алкил, моно- или ди-(С1-С6алкил)аминоС0-С6алкил, моно- или ди-(С1-С6алкил)аминокарбонил, (С3-С7циклоалкил)С0-С6алкил, или (от 4- до 7-членный гетероциклоалкил)С0-С6алкил; или (ii) взятый вместе с R2 образует конденсированный 5- или 6-членный карбоцикл или гетероцикл, каждый из которых является замещенным 0-3 заместителями, независимо выбранными из галогена, гидрокси, нитро, циано, амино, С1-С4алкил, С1-С4 алкокси, галогенС1-С4алкил и галогенС1-С4алкокси; R2 представляет собой галоген ...

СПОСОБ ПОЛУЧЕНИЯ 1,4-БУТАНДИОЛА

Использование: в производстве 1,4-бутандиола, применяемого для получения сложных полиэфиров, полиуретанов, эпоксидных смол. Раскрывается способ получения 1,4-бутандиола, в котором 2, 5-дигидрофуран в одну стадию подвергают взаимодействию с водой и водородом при температуре 20-300oC и давления 1-300 бар, в присутствии катализатора гидрирования. Одностадийный способ обеспечивает большой выход целевого продукта при хорошей избирательности и конкурентноспособную цену. 10 з.п.ф-лы, 1 табл.

ЛЕКАРСТВЕННЫЙ КОНЪЮГАТ ПРОИЗВОДНОГО ЭРИБУЛИНА, СПОСОБ ЕГО ПОЛУЧЕНИЯ И ЕГО ПРИМЕНЕНИЕ В МЕДИЦИНЕ

Группа изобретений относится к области биотехнологии и может быть использована в медицине. Раскрывается конъюгат антитела, нацеленного на опухолевый антиген, с производными эрибулина – воздействующими на тубулин цитотоксическими агентами, препятствующими нормальному протеканию митоза клеток. Изобретение может быть применимо в терапии различных злокачественных новообразований. 6 н. и 50 з.п. ф-лы, 7 пр., 11 табл., 2 ил.

ГИДРОКСИЭТИЛАМИНОСУЛЬФОНАМИДЫ, ПРОМЕЖУТОЧНЫЕ СОЕДИНЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СПОСОБ ИНГИБИРОВАНИЯ РЕТРОВИРУСНЫХ ПРОТЕАЗ, СПОСОБ ЛЕЧЕНИЯ РЕТРОВИРУСНЫХ ИНФЕКЦИЙ, СПОСОБ ЛЕЧЕНИЯ СПИДА

В изобретении предлагаются гидроксиэтиламиносульфонамидные соединения α- и b-аминокислот, эффективные в качестве ингибиторов ретровирусных протеаз и, в частности, в качестве ингибиторов протеазы ВИЧ, а также фармацевтические композиции.

СПОСОБЫ ПОЛНОГО СИНТЕЗА РЕЗОЛВИНА E1

СПОСОБЫ ПОЛУЧЕНИЯ 2'-ФТОР-2'-АЛКИЛЗАМЕЩЕННЫХ ИЛИ ДРУГИХ ЗАМЕЩЕННЫХ РИБОФУРАНОЗИЛПИРИМИДИНОВ И ПУРИНОВ И ИХ ПРОИЗВОДНЫХ

... 1. Способ синтеза 2'-дезокси-2'-фтор-2'-С-метил-β-D-рибофуранозил нуклеозидов формулы 14включающий следующие стадии:(а) восстановление лактона формулы 49до соответствующего сахара с последующим ацетилированием с получением соединения формулы 54В, где L обозначает любую удаляемую группу,(b) конденсация продукта 54В со стадии (а) с силилированным основанием в присутствии катализатора с образованием смеси защищенных нуклеозидов 55 и 55-α(c) разделение аномеров 55 и 55-α, полученных на стадии (b) и(d) снятие защиты у защищенного нуклеозида 55 со стадии (с) с получением желаемого нуклеозида.2. Способ по п.1, отличающийся тем, что силилированное основание на стадии (b) представляет собой силилированный N4-бензоилцитозин, снятие защиты которого осуществлено при помощи алкоголята металла в среде спирта.3. 3,5-ди-О-защищенный 2-дезокси-2-фтор-2-С-метил-D)-рибоно-γ-лактон общей формулыгде Rи Rмогут независимо обозначать Н, СН, Ac, Bz, пивалоил или 4-нитробензоил, 3-нитробензоил, 2-нитробензоил, 4 ...

Способ получения транс-2-замещенных 5-арил-2,3,4,4а,5,9 @ -гексагидро-1 @ -пиридо (4,3- @ ) индолов

... 1. СПОСОБ ПОЛУЧЕНИЯ ТРАНС-2-ЗАМЕЩЕННЫХ 5-АРШ1-2,3,4,4а, 3,9Ъ-ГЕКСАгадРО-1Н-ПИРИДО ...

SULFONAMIDDERIVATE ALS ASPARTYLPROTEASE-INHIBITOREN

Hydroxyethylaminosulfonamide verwendbar als Inhibitoren retroviraler Proteasen

VERFAHREN ZUR HERSTELLUNG SUBSTITUIERTER CYCLOPROPANCARBALDEHYDE.

Sulfonamid inhibitoren von Hiv-aspartyl Protease

Verfahren zur Herstellung von Anhydrozuckeralkoholen

A process is described for continuous production of anhydrosugar alcohols by continuous introducing of sugar alcohols and/or monoanhydrosugar alcohols into a reaction vessel and dehydration in the presence of an acid catalyst and solvent, preferably an organic solvent, in which the resultant reaction products are soluble. Water and the organic solvent having the dissolved reaction product are each continuously removed from the reaction chamber. The reaction product is separated from the removed solvent, which is recycled into the reaction vessel. The reaction product is optionally purified by distillation and/or recrystallization. The purified reaction product obtained is particularly suitable as a starting product for producing polymers, and has a purity of at least 99.0 %.

HETEROCYCLISCHE VERBINDUNGEN.

TETRAHYDROFURANYL (THF) ENTHALTENDE SULFONAMIDINHIBITOREN DER ASPARTYL-PROTEASE

HEMMUNG DER p38 KINASE UNTER VERWENDUNG VON SYMMETRISCHEN UND ASYMMETRISCHEN DIPHENYLHARNSTOFFEN

NEUE 16,17-SECOOESTRADI- UND TRIENE VERFAHREN ZU IHRER HERSTELLUNG SOWIE DIESE ENTHALTENDES MITTEL

Neue 16,17-Secosteroide und Verfahren zu ihrer Herstellung

B,D-SECO-DELTA4 AND DELTA5,10-STEROIDAL COMPOUNDS

... 1350730 B,D - diseco - #4 and #5(10) - steroids SYNTEX CORP 16 June 1972 [20 July 1971] 28318/72 Heading C2C [Also in Division C7] Novel disecosteroids of the estrane series having the formulµ (wherein R1 is free or esterified -CO 2 H, -COCH 3 or C 1-4 alkyl or is -CH 2 OH in which the OH group may be etherified or esterified and in which the -CH 2 - group may be substituted by one or two C 1-4 alkyl groups or by one C 1-4 alkyl group and a phenyl group) are prepared as illustrated in the following reaction scheme wherein R3 and R5 are C 1-4 alkyl, R4 is C 1-4 alkyl or phenyl and R6 is H or C 1-4 alkyl. (I) is reduced with a double metal hydride to (II), this is Birch reduced to a 3-methoxy-#2,5(10)- diene and this is hydrolysed to (III), mild hydrolysis giving a #5(10)-3-one and hydrolysis with a strong acid giving a #4-3-one. (III) is oxidized with CrO 3 to (IV) (R6=H) which may then be ...

Tetrahydrofuran derivatives

This invention relates to: (a) new tetrahydrofuran derivatives having the general formula I: I wherein either each of R and R' independently represents a hydrogen atom or various hydrocarbon substituents and A represents either a nitrogen containing ring or an alkylammonium salt or an alkylaminoacid rest; (b) a process for the preparation of said compounds and (c) therapeutic compositions containing said compounds as an active ingredient.

TETRAHYDROFURAN DERIVATIVES

HERBICIDAL TETRAHYDROFURAN DERIVATIVES

Crystalline enzyme inhibitor compound

PROCESS

Method for the preparation of hexahydro-furo [2,3-B]furan-3-o1.

Methods for the preparation of (3R,3aS,6aR) hexahydro-furo !2,3-b!furan-3-ol

Sulphonamide derivatives as prodrugs of aspartyl proteaseinhibitors

Methods for the preparation of (3R,3aS,6aR) hexahydro-furo !2,3-b!furan-3-ol

Substituted hydroxyethylamines

Oxygenated heterocycle containing sulfonamide inhibitors of aspartyl protease.

The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting fflV-1 and HIV-2 protease activity and consequently, may be advantageously used as anu-v.ral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention.

Process for the synthesis of HIV protease inhibitors.

An improved for the synthesis of (3S)-tetrahydro-3-furyl N-[(1S,2R)-3-(4-amino-n-isobutylbenzenesulphonamido)-1-benzyl-2-hydroxypropyl]carbamate comprising four steps from the compound of formula (A) and a novel intermediate thereto.

THF-containing sulfonamide inhibitors of aspartyl protease.

The present invention relates to a class of TKF-containing sulfonamide aspartyl protease inhibitors having the structure of formula I: D OH D1 I I ITHF—R-NH—CH—CH—CH2——N—S02E (I) . This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention.

Method for the preparation of hexahydro-furo [2,3-b]furan-3-ol.

The present invention relates to a method for the preparation of hexahydro-furo[2,3-b]furan-3-ol as well as novel intermediates for use in said method. More in particular the invention relates to a stereoselective method for the preparation of hexahydro-furo[2,3-b]furan-3-ol, and to a method amenable to industrial scaling up.

Sulfonamide inhibitors of aspartyl protease.

The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention and methods for screening compounds for anti-HIV activity.

Novel sulfonamide inhibitors aspartyl protease.

The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of hiv aspartyl protease inhibitors characterized by specific structural and characterized by specific structural and physicochemical features this invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting hiv-1 and hiv-2 protease activity and consequently, may be advantageously used as anti-viral agents against the hiv-1 and hiv-2 viruses. This invention also relates to methods for inhibiting the activity of hiv aspartly protease using the compounds of this invention and methods for screening compounds for ant-hiv activity ...

Substituted hydroxyethylamines

Methods for the preparation of (3R,3aS,6aR) hexahydro- furo [2,3-b] furan-3-ol

Sulphonamide derivatives as prodrugs of aspartyl proteaseinhibitors

Process for the synthesis of hiv protease inhibitors

Oxygenated heterocycle containing sulfonamide inhibitors of aspartyl protease

Sulfonamide inhibitors of aspartyl protease

THF-containing sulfonamide inhibitors of aspartyl protease

Prodrugs of aspartyl protease inhibitors.

The present invention relates to prodrugs of a class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of prodrugs of hiv aspartyl protease inhibitors characterized by favorable aqueous solubility, high oral bioavailability and facile in vivo generation of the active ingredient. This invention also relates to pharmaceutical compositions comprising these prodrugs. The prodrugs and pharmaceutical compositions of this invnetion are particularly well suited for decreasing the pill burden and increasing patient compliance. This invention also relates to methods of treating mammals with these prodrugs and pharmaceutical compositions.

NOVEL SULFONAMIDE INHIBITORS OF ASPARTYL PROTEASE

NOVEL PIPERAZINE

A compound of formula (1)or the pharmaceutically acceptable salt thereof; wherein a,b,c,d,e,j,R1,R2,R3, and R4, are as defined above useful to treat inflammation and other immune disorders.

Method for the preparation of hexahydro-furo [2,3-B]furan-3-o1.

N,N' -substituted-1,3-diamino -2-hydroxypropane derivatives.

Disclosed are compounds of the formula (0, wherein the variables RN, RC, R1, R25, R2, and R3 are as defined herein. These compounds have activity as inhibitors of betasec-retase and are therefore useful in treating a variety of discorders such as Alzheimer's Disease.

Methods for the preparation of (3R,3aS,6aR) hexahydro-furo !2,3-b!furan-3-ol

Oxygenated heterocycle containing sulphonamide inhibitors of aspartyl

Sulphonamide derivatives as prodrugs of aspartyl proteaseinhibitors

Sulphonamide derivatives as prodrugs of aspartyl protease inhibitors.

The present invention relates to prodrugs of a class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class prodrugs of hiv aspartyl protease inhibitors characterized by favorable aqueous solubility, high oral bioavailability and facile in vivo generation of the active ingredient. This invention also relates to pharmaceutical compositions comprising these prodrugs. The prodrugs and pharmaceutical compositions of this invention are particularly well suited for decreasing the pill burden and increasing, patient compliance. This invention also relates to methods of treating mammals with these prodrugs and pharmaceutical compositions.

Substituted hydroxyethylamines

Sulphonamide derivatives as prodrugs of aspartyl protease inhibitors.

Sulfonamide inhibitors of aspartyl protease.

Composed with groupings triazole or imidazol and tétrahydrofuranne, use of those as fungicides and methods of preparation.

N,N'-substituted-1,3-diamino-2-hydroxypropane derivatives.

Fungicidical N-phenylcarbamates.

Novel piperazine derivatives.

Substituted hydroxyethylamines.

New derivatives oxy-5 of the tétrahydrofurane, a process for their preparation and compositions therapeutic while containing.

Fungicides with triazole groups and oligoéther.

Prodrugs of aspartyl protease inhibitors

Oxygenated heterocycle containing sulfonamide inhibitors of aspartyl protease

Process for the synthesis of hiv protease inhibitors

THF-containing sulfonamide inhibitors of aspartyl protease

Sulfonamide inhibitors of aspartyl protease

Novel piperazine derivatives

Method for the preparation of hexahydro-furo [2,3-B]furan-3-o1.

NOVEL SULFONAMIDE INHIBITORS OF ASPARTYL PROTEASE

Process for the synthesis of hiv protease inhibitors

Sulfonamide inhibitors of aspartyl protease

Novel piperazine derivatives

PROCEDURE FOR the PRODUCTION OF 1 (2 ' - FURANIDYL) 5-FLUORURACIL

SULFONE AMIDE DERIVATIVES AS ACTIVE SUBSTANCE FORERUNNERS OF INHIBITORS THE ASPARTYL PROTEASE ONES

HERBICIDES COMPOSITIONS

HERBIZIDES MITTEL

PROCEDURE FOR THE PRODUCTION OF HEXAHYDROFUROC2,3BÜFURAN-3-OL

VERFAHREN ZUR HERSTELLUNG VON NEUEN, SUBSTITUIERTEN TETRAHYDROFURANEN

VERFAHREN ZUR AROMATISIERUNG VON LEBENSMITTELN

N ((3-BENZYL) - 2,2 (UNTIL PHENYL) - PROPAN-1AMINDERIVATE AS CETP HEMMER FOR the TREATMENT OF ATHEROSKLEROSE AND HEART CYCLE ILLNESSES

DIOXANONDERIVATE ON PLANT BASIS, SYNTHESIS AND USE OF IT

PROCEDURE FOR AROMATIZING OF FOOD

NEW FLUORHALTIGE CONNECTION, FLUORHALTIGES POLYMER AND PROCEDURE FOR THE PRODUCTION OF THE CONNECTION

PROCEDURE FOR THE PRODUCTION OF ERYTHROBISHYDROXYALKENSA¨RE DERIVATIVES.

NEUE 5-OXY-TETRAHYDROFURANDERIVATE

PHARMACEUTICAL ACTIVE CONNECTIONS.

PROCEDURE FOR VERAETHERUNG OF HEXITOLEN AND ANHYDROHEXITOLEN.

HERBICIDE MEANS

D-MANNOSEODER XYLITO ESTER AND THEIR VERWENUNG THAN DRUGS

PURINYL AND PYRIMIDINYL TETRAHYDROFURANES.

PROCEDURE FOR the PRODUCTION OF 1,4-BUTANDIOL

AZOLYLMETHYL TETRAHYDROFURANES OF DERIVATIVES, AS PLANT WAX MODULATORS AND FUNGICIDES.

NEW CRYSTALLINE ONES OF SALTS OF ARYLOXYPROPANOLAMINEN, PROCEDURES FOR YOUR PRODUCTION AND YOUR USE.

PROCEDURE FOR the PRODUCTION OF 5-HYDROXY-3HYDROXYMETHYL-PHENYLFURAN-DERIVATEN.

N-PHENYLCARBAMATE ONE WITH FUNGICIDAL EFFECT.

SULFONE AMIDE DERIVATIVES AS ASPARTYLPROTEASE INHIBITORS

ASPARTYL PROTEASE INHIBITORS

Procedure for the production new secondary p-Aminophenylamidine as well as their acid addition salts

Procedure for the production new secondary p-Aminophenylamidine as well as their acid addition salts

Synthesis of ttx intermediates

The present invention relates to the synthesis of intermediates which are useful in TTX synthesis and to the preparation thereof.

Viral polymerase inhibitors

Compounds of formula I: wherein X, R 2 , R 3 , R 3a , R 3b , R 5 and R 6 are defined herein, are useful as inhibitors of the hepatitis C virus NS5B polymerase.

Process for preparation of substantially pure fosamprenavir calcium and its intermediates

The present invention relates to fosamprenavir calcium (Ia) substantially free of isomer impurity, (3R) tetrahydro -3 -furanyl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-(phosphonooxy)propyl carbamate (Ib), and its process for preparation thereof. The present invention also provides fosamprenavir calcium intermediate, (S)-3-tetrahydrofuranyl-N-succinimidyl carbonate (IIa) substantially free of (R)-3-tetrahydrofuranylsuccinimidyl carbonate (IIb) and its process for preparation thereof.

N-((3-BENZYL)-2,2-(BIS-PHENYL)-PROPAN-1-AMINE DERIVATIVES AS CETP INHIBITORS FOR THE TREATMENT OF ATHEROSCLEROSIS AND CARDIOVASCULAR DISEASES

Compounds of formula Ia and Ib 2. The compound of claim 1 , wherein A is:{'sub': 1', '6', '40', '46', '1', '6', '29', '30', '40', '40', '40', '40', '40', '40', '1', '6, "(a) phenyl, which is substituted with one or more substituents selected from the group consisting of: 1) halo, 2) (C-C)-alkyl, which may be optionally substituted with one or more R's, 3) —OR, 4) (C-C)-alkylthio, 5) cyano, 6) nitro, 7) —NRR, 8) aryl, which may be optionally substituted with one or more R's, 9) arylalkyl, which may be optionally substituted with one or more R's, 10) heteroaryl, which may be optionally substituted with one or more R's, 11) heteroarylalkyl, which may be optionally substituted with one or more R's, 12) heterocyclyl, which may be optionally substituted with one or more R's, 13) heterocyclylalkyl, which may be optionally substituted with one or more R's, 14) halo(C-C)alkyl,"}{'sub': 46', 'p', '46', '2', '46', '46, '15) —COR, 16) ═O, 17) —S(O)R, 18) —SONHR, 19) —COOR,'}{'sub': 46', '46', '46', '2', '6', '40', '2', '6', '40', '46', '46', '46', '46', '40, "20) —NHC(CN)NHR, 21) —CONRR, 22) (C-C)-alkynyl, which may be optionally substituted with one or more R's, 23) (C-C)-alkenyl, which may be optionally substituted with one or more R's, 24) —OCOR, 25) —OCOOR, or 26) —OCONRR; or any two adjacent substituents may join together to form a 4- to 8-membered ring, which optionally may contain 1-4 heteroatoms selected from N, O, and S and be optionally substituted with one or more R's;"}{'sub': 1', '6', '40', '46', '1', '6', '29', '30', '40', '40', '40', '40', '40', '40', '1', '6, "(b) heteroaryl, which is substituted with one or more substituents selected from the group consisting of: 1) halo, 2) (C-C)-alkyl, which may be optionally substituted with one or more R's, 3) —OR, 4) (C-C)-alkylthio, 5) cyano, 6) nitro, 7) —NRR, 8) aryl, which may be optionally substituted with one or more R's, 9) arylalkyl, which may be optionally substituted with one or more R's, 10) heteroaryl, which ...

Intermediates useful for the synthesis of fexofenadine, processes for their preparation and for the preparation of fexofenadine

Intermediates useful for the synthesis of fexofenadine, processes for their preparation and processes for the synthesis of fexofenadine are described.

PROCESS FOR THE PREPARATION OF (3R, 3AS, 6AR)-HEXAHYDROFURO [2, 3- B] FURAN-3-OL

The present invention relates to a novel process for the preparation of (3R, 3aS, 6aR)-hexahydrofuro[2, 3-b]furan-3-ol of formula I by reacting a compound of formula VII with the compound of formula R2-OH in the presence of haloginating agent to obtain a compound of formula VI and treating a compound of formula VI with dehaloginating agent to obtain a compound of formula V by reducing a compound of formula V, followed by cylization to obtain compound of formula IV and separating the enantiomer and diastereomers from compound of formula IV to yield a compound of formula I. Compound of formula I is useful as an intermediate in the preparation of protease inhibitors, in particular broad spectrum HIV protease inhibitors, the present invention also relates to process for the preparation of Darunavir from (3R, 3aS, 6aR)-hexahydrofuro[2, 3-b]furan-3-ol. 127.-. (canceled)30. The process according to or , wherein the step of separating the enantiomers and diasteromers of the compound of formula IV to obtain the compound of formula I is carried out via an enzymatic or a chemical process.32. The process according to claim 31 , wherein the catalyst used in step a) is N claim 31 ,N-dimethylamino pyridine.36. The process according to further comprising resolving or separating the enantiomers of the compound of formula IV to obtain the compound of formula I.3735. The process according to claim 35 , claim 35 , claim 35 , or claim 35 , wherein the compound of formula I is used as an intermediate in the preparation of HIV protease inhibitors.38. The process according to claim 37 , wherein the HIV protease inhibitor is Darunavir. This application claims priority to Indian patent application No 3518/CHE/2010 filed on Nov. 22, 2010 the contents of which are incorporated by reference in their entirety.The present invention relates to a process for the preparation of (3R, 3aS, 6aR)-hexahydrofuro[2, 3-b]furan-3-ol, which is useful as an intermediate in the preparation of protease ...

Agrochemical Adjuvants and Formulations

Ethoxylated fatty acid mono-ester(s) of sorbitan with a fatty acid chain length from 8 to 14 and an overall degree of ethoxylation from 7 to 16 are new (though related to the polysorbates). These compounds are useful as adjuvants in agrochemical formulations, particularly combination formulations of herbicides having differing weed control effects, notably of non-selective herbicide and selective herbicide; particularly selective herbicide, particularly selective broadleaf herbicide, and graminicide; and selective graminicide and non-selective herbicide, especially a combination of a glyphosate type non-selective water soluble herbicide with a clethodim type selective (graminicide) herbicide, particularly to reduce or eliminate antagonism between differing types of herbicide. Formulations including such herbicide combinations and the adjuvant compounds are particularly useful in controlling weed including volunteer glyphosate resistant maize in subsequently sown glyphosate resistant soya. 1. A compound or mixture of compounds which is/are ethoxylated fatty acid mono-ester(s) of sorbitan in which the carbon chain length of the fatty acid is from 8 to 14 and the overall degree of ethoxylation is on average from 7 to 16.2. A compound or mixture of compounds according to claim 1 , where the ester(s) are compounds of formula (I):{'br': None, 'sub': n1', 'n2', 'n3', 'n4, 'sup': 1', '2', '3', '4, 'Sorb-(EOR)(EOR)(EOR)(EOR)\u2003\u2003(I)'} i) Sorb represents a residue obtained by removing four hydroxyl H atoms from sorbitan;', 'i) EO represents an ethyleneoxy residue;', 'ii) n1, n2, n3, and n4 each independently represent average values from 0 to 10;', 'iii) the total n1+n2+n3+n4 has an average value from 7 to 16; and', {'sup': 1', '2', '3', '4', '5', '5, 'sub': 7', '13, 'iv) R, R, R, and Reach independently represents H or an acyl group —C(O)—R, where Ris a Cto Chydrocarbyl.'}], 'wherein;'}3. A compound or mixture of compounds according to claim 2 , wherein an average of ...

DIAZENIUMDIOLATE HETEROCYCLIC DERIVATIVES

A compound having the structure: useful for treating hypertension, Pulmonary Arterial Hypertension (PAH), congestive heart failure, conditions resulting from excessive water retention, cardiovascular disease, diabetes, oxidative stress, endothelial dysfunction, cirrhosis, pre-eclampsia, osteoporosis or nephropathy. 4. A compound of claim 1 , wherein Ris hydrogen claim 1 , —C(O)OH claim 1 , or —C(O)OCH claim 1 , or a pharmaceutically acceptable salt thereof.5. A compound of claim 1 , wherein Ris hydrogen claim 1 , or a pharmaceutically acceptable salt thereof.6. A compound of claim 1 , wherein Ris —CDCalkyl claim 1 , —C(CH) claim 1 , —CHCH claim 1 , or —CH(CH).8. A compound of claim 1 , wherein Ris hydrogen claim 1 , —CH claim 1 , C(O)OCH claim 1 , —C(O)OH claim 1 , phenyl claim 1 , or a pharmaceutically acceptable salt thereof.9. A compound of claim 1 , wherein Ris hydrogen or —CH claim 1 , or a pharmaceutically acceptable salt thereof.10. A compound of claim 1 , wherein Rand Rare attached to the same carbon atom and together form ═O claim 1 , or a pharmaceutically acceptable salt thereof.16. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CHor —CH.17. A compound of claim 1 , wherein Rand R claim 1 , together with the N atom to which they are attached claim 1 , form a 5- or 6-membered heterocyclic ring containing 1 N atom claim 1 , which ring is unsubstituted or substituted with —CHOH.18. A compound of claim 1 , wherein Rtogether with R claim 1 , forms ═O.19. A compound of claim 1 , which is{'sup': '2', 'O-[(3R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl]1-(N-tert-butyl-N-methylamino)diazen-1-ium-1,2-diolate,'}{'sup': '2', 'O-[(3S)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl]1-(N-tert-butyl-N-methylamino)diazen-1-ium-1,2-diolate,'}{'sup': '2', 'O-[(3R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl]1-(N-tert-butyl-N-ethylamino)diazen-1-ium-1,2-diolate,'}{'sup': '2', 'O-[(3R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl]1-(N-tert-butyl-N- ...

NOVEL 3,6-ANHYDRO-L-GALACTOSE DEHYDROGENASE ACTING ON 3,6-ANHYDRO-L-GALACTOSE, AND PRODUCTION OF 3,6-ANHYDROGALACTONIC ACID BY USING THE ENZYME

The present invention relates to a novel 3,6-anhydro-L-galactose dehydrogenase and to a novel compound produced therefrom. More specifically, provided is a 3,6-anhydro-L-galactose dehydrogenase which can produce 3,6-anhydrogalactonic acid of a novel type by metabolizing 3,6-anhydro-L-galactose. 1. 3 ,6-anhydro-L-galactose dehydrogenase having amino acid sequence as set forth in SEQ ID NOs: 1 to 4.2. A gene encoding 3 claim 1 ,6-anhydro-L-galactose dehydrogenase of .3. The gene of claim 2 , wherein the gene has sequences as set forth in SEQ ID NOs: 5 to 8.4. A recombinant vector containing the gene encoding 3 claim 2 ,6-anhydro-L-galactose dehydrogenase of .5. The recombinant vector of claim 4 , wherein the gene has sequences as set forth in SEQ ID NOs: 5 to 8.6. A transformant which is transformed with the recombinant vector of .7. A method of producing 3 claim 6 ,6-anhydro-L-galactose dehydrogenase which includes a step of obtaining 3 claim 6 ,6-anhydro-L-galactose dehydrogenase from a culture of the transformant of .9. The method of producing the compound of chemical formula 1 of claim 8 , wherein 3 claim 8 ,6-anhydro-L-galactose dehydrogenase has any one of amino acid sequences as set forth in SEQ ID NOs: 1 to 4.10. The method of producing the compound of the chemical formula 1 of claim 9 , wherein 3 claim 9 ,6-anhydro-L-galactose dehydrogenase is encoded by any one of sequences as set forth in SEQ ID NOs: 5 to 8. This application claims priority to and the benefit of Korean Patent Application No. 2011-0006631, filed Jan. 24, 2011, the disclosure of which is incorporated herein by reference in its entirety.1. Field of the InventionThe present invention relates to 3,6-anhydro-L-galactose dehydrogenase which produces a novel 3,6-anhydrogalatonic acid by metabolizing 3,6-anhydro-L-galactose as a bio energy production technology.2. Discussion of Related ArtThe world is currently facing depletion and rises in prices of petroleum resources, which are a major energy ...

ANTIOXIDANT INFLAMMATION MODULATORS: OLEANOLIC ACID DERIVATIVES WITH AMINO AND OTHER MODIFICATIONS AT C-17

This invention provides, but is not limited to, novel oleanolic acid derivatives having the formula: 34-. (canceled)710-. (canceled)11. The compound of claim 5 , wherein either Xor Xis OR claim 5 , wherein Ris absent.12. The compound of claim 6 , wherein Xis ORand Ris absent.13. The compound of claim 5 , wherein Xis hydrogen.14. (canceled)15. The compound of claim 6 , wherein Y is NRR.1617-. (canceled)18. The compound of claim 6 , wherein Ror Rcomprises a fluoro group.19. The compound of claim 18 , wherein one of Ror Rcomprises a trifluoromethyl group.20. The compound of claim 6 , wherein Rand Rare each independently hydrogen claim 6 , alkyl claim 6 , aryl claim 6 , aralkyl claim 6 , heteroaryl claim 6 , heteroaralkyl claim 6 , or a substituted version of any of these groups.2123-. (canceled)24. The compound of claim 6 , wherein Ris alkylsulfonyl claim 6 , arylsulfonyl claim 6 , aralkylsulfonyl claim 6 , heteroarylsulfonyl claim 6 , heteroaralkylsulfonyl claim 6 , or a substituted version of any of these groups.2529-. (canceled)30. The compound of claim 6 , wherein Ris acyl.31. The compound of claim 6 , wherein Ris substituted acyl.32. (canceled)33. The compound of claim 6 , wherein R′ is cyano.34. (canceled)35. The compound of claim 2 , wherein Ris absent.3637-. (canceled)38. The compound of claim 6 , wherein Rand Rare each methyl.39. The compound of claim 5 , wherein Rand Rare each hydrogen.40. The compound of claim 2 , wherein the bond joining carbon 1 and carbon 2 is a double bond.41. The compound of claim 6 , wherein the bond joining carbon 9 and carbon 11 is a double bond.42. The compound of claim 6 , wherein the bond joining carbon 9 and carbon 11 is a single bond.43. The compound of claim 5 , wherein the bond joining carbon 12 and carbon 13 is a single bond.44. The compound of claim 5 , wherein the bond joining carbon 13 and carbon 18 is a single bond.45. (canceled)47. (canceled)49. (canceled)51. (canceled)53. (canceled)55. (canceled)57. (canceled)59. ( ...

Indanyloxyphenylcyclopropanecarboxylic acids

The present invention relates to compounds of general formula I, wherein the groups R 1 , R 2 , R 3 , m and n are defined as in claim 1 , which have valuable pharmacological properties, in particular bind to the GPR40 receptor and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2. Furthermore, the invention relates to novel intermediates, useful for the synthesis of compounds of formula I.

Squarylated Lactones Inhibitors for Bacterial Biofilm Formation

A library of unnatural squarylated homoserine lactones (SHLs) and squarylated lactones that bear potential to modulate biofilm formation in Gram negative bacteria. At low concentrations (˜200 μM), these small molecules inhibit biofilm formation of . Moreover, these compounds are not toxic up to 300 μM and do not significantly attenuate growth. The SHLs have potential to disperse established biofilm and demonstrate an enhanced reduction (˜50%) of the maximum biofilm thickness by use of SHLs during biofilm growth. 2. The squarylated homoserine lactone of claim 1 , wherein said squarylated homoserine lactone is characterized by an ability to modulate quorum sensing.3. The squarylated homoserine lactone of claim 1 , wherein said squarylated homoserine lactone is characterized by an ability to inhibit biofilms.6. The squarylated homoserine lactone of claim 5 , wherein said squarylated homoserine lactone is characterized by an ability to modulate quorum sensing.7. The squarylated homoserine lactone of claim 5 , wherein said squarylated homoserine lactone is characterized by an ability to inhibit biofilms.8. A method of producing a squarylated homoserine lactone claim 5 , comprising the steps of:(a) subjecting 3,4-dibutoxy-cyclobut-3-ene-1,2-dione to Grignard/organolithium reagents to produce a 1,2 addition reaction; and(b) treating the product of step (a) with trifluoroacetic anhydride;(c) performing hydrolysis of the product of step (b) to produce a squarylated ester intermediate; and(d) treating said squarylated ester intermediate with and α-Amino-γ-butyrolactone to produce a squarylated homoserine lactone.10. The method of claim 9 , wherein said squarylated homoserine lactone is characterized by an ability to modulate quorum sensing.11. The method of claim 9 , wherein said squarylated homoserine lactone is characterized by an ability to inhibit biofilms.14. The method of claim 8 , wherein said squarylated homoserine lactone is characterized by an ability to modulate ...

PROCESS FOR CONVERTING POLYSACCHARIDES IN AN INORGANIC MOLTEN SALT HYDRATE

A process is disclosed for converting polysaccharides to platform chemicals. The process comprises dissolving the polysaccharides in a inorganic molten salt hydrate, converting the polysaccharides to monosaccharides, and converting the monosaccharides to platform chemicals that are easily separable from the inorganic molten salt hydrate. 128.-. (canceled)29. A process for converting ligno-cellulosic biomass to platform chemicals , said process comprising the steps of:a) dissolving ligno-cellulosic biomass in an inorganic molten salt hydrate;b) converting the dissolved ligno-cellulosic biomass to monosaccharides;c) converting the monosaccharides to platform chemicals that are easily separable from the inorganic molten salt hydrate;d) separating the platform chemicals from the inorganic molten salt hydrate.30. The process of claim 29 , further comprising: pre-treating the lignocellulosic biomass through comminution claim 29 , or subjecting the ligno-cellulosic biomass to comminution during step a).31. The process of claim 29 , wherein the molten salt hydrate comprises a composition claim 29 , the composition comprising at least Zn claim 29 , Ca or Li halides claim 29 , or mixtures thereof claim 29 , with a content of 40 to 80 wt % of salt in said composition.32. The process of claim 29 , wherein in step b) claim 29 , the acid is an inorganic soluble acid.33. The process of claim 29 , wherein lignin is separated out after step b).34. The process of claim 29 , wherein acid is removed prior to step c).35. The process of claim 29 , wherein step c) takes place in a fixed bed catalyst claim 29 , slurry reactor claim 29 , expanded bed catalyst claim 29 , moving bed catalyst claim 29 , or trickle bed catalyst.36. The process of claim 29 , wherein the hydrogenation catalyst is selected from a noble metal of the series of Ru claim 29 , Rh claim 29 , Pd and Pt claim 29 , or a transition metal of the series Cu claim 29 , Cr claim 29 , Co claim 29 , Ni and Fe.37. The process of ...

METHODS AND COMPOSITIONS FOR TREATING METABOLIC SYNDROME

Provided are methods, compositions, systems, and kits for treating metabolic syndrome or a disorder associated with metabolic syndrome, e.g., obesity, dyslipidemia, and/or a diabetic condition, comprising administering systemically to a subject one or more compounds of the Formula (I) and/or (II): or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, polymorph, tautomer, isotopically enriched derivative, or prodrug thereof, wherein, L, R; R, Z, X, A and B are defined herein. 3. The method of claim 1 , wherein the disorder associated with metabolic syndrome is obesity.4. The method of where the method reduces adipocytes in the subject.5. The method of wherein the disorder associated with metabolic syndrome is dyslipidemia.6. The method of claim 5 , wherein the method reduces triglycerides claim 5 , reduces LDL claim 5 , reduces total cholesterol claim 5 , and/or increases HDL in the subject.7. The method of wherein the disorder associated with metabolic syndrome is a diabetic condition.8. The method of claim 7 , wherein the diabetic condition is type 2 diabetes mellitus.9. The method of claim 8 , wherein the method reduces serum glucose claim 8 , reduces glycated hemoglobin claim 8 , reduces serum insulin claim 8 , improves glucose tolerance claim 8 , reduces the subject's need for insulin claim 8 , and/or reduces the incidence of a diabetic complication in the subject.10. The method of claim 1 , wherein the subject suffers from or is likely to suffer from a disease claim 1 , disorder or condition selected from the group consisting of metabolic syndrome claim 1 , overweight claim 1 , obesity claim 1 , dyslipidemia claim 1 , hypercholesterolemia claim 1 , hypertriglyceridemia claim 1 , diabetes mellitus claim 1 , vascular disease claim 1 , atherosclerosis claim 1 , coronary artery disease claim 1 , stroke claim 1 , cerebrovascular disease claim 1 , peripheral vascular disease claim 1 , fatty liver claim 1 , pancreatitis claim 1 , inflammation or ...

SYNTHESIS OF AN ANTIVIRAL COMPOUND

The present disclosure provides processes for the preparation of a compound of Formula I: 5. The process of claim 3 , wherein the N-arylation reaction conditions comprise a catalyst.6. The process of claim 5 , wherein the catalyst is a palladium claim 5 , platinum claim 5 , or copper based catalyst.7. The process of claim 6 , wherein the catalyst is selected from the group consisting of tris(dibenzylideneacetone)dipalladium(0) claim 6 , copper(I) chloride claim 6 , copper(II) chloride claim 6 , copper(I) bromide claim 6 , copper(II) bromide claim 6 , copper(I) acetate claim 6 , copper(II) acetate claim 6 , copper(II) acetylacetonate claim 6 , copper(I) trifluoromethanesulfonate claim 6 , copper(II) trifluoromethanesulfonate claim 6 , copper(I) thiophene-2-carboxylate claim 6 , and copper(I) iodide.8. The process of claim 3 , wherein the N-arylation reaction conditions further comprise a ligand.9. The process of claim 8 , wherein the ligand is selected from the group consisting of 5-(di-tert-butylphosphino)-1′ claim 8 ,3′ claim 8 ,5′-triphenyl-1′H-[1 claim 8 ,4]bipyrazole claim 8 , 2-(di-tert-butyl-phosphino)-1-phenyl-1H-pyrrole claim 8 , 2-(di-tert-butylphosphino)-1-(2-methoxyphenyl)-1H-pyrrole claim 8 , acetylacetone claim 8 , acetylcyclohexanone claim 8 , isobutyrylcyclohexanone claim 8 , N claim 8 ,N-dimethylcyclohexane-1 claim 8 ,2-diamine claim 8 , L-proline claim 8 , BINAP claim 8 , and N claim 8 ,N-diethylsalicylamide.10. The process of claim 3 , wherein the N-arylation reaction conditions comprise a base.11. The process of claim 10 , wherein the base is selected from the group consisting of potassium hydroxide claim 10 , sodium hydroxide claim 10 , sodium tert-amylate claim 10 , cesium carbonate claim 10 , cesium hydroxide claim 10 , potassium phosphate tribasic claim 10 , sodium tertbutoxide claim 10 , sodium methoxide claim 10 , and sodium ethoxide.12. The process of claim 3 , wherein the N-arylation reaction conditions comprise a phase transfer catalyst. ...

ANTIOXIDANT INFLAMMATION MODULATORS: OLEANOLIC ACID DERIVATIVES WITH AMINO AND OTHER MODIFICATIONS AT C-17

This invention provides, but is not limited to, novel oleanolic acid derivatives having the formula: 1257-. (canceled)259264-. (canceled)266. The method of claim 265 , wherein Ris hydrogen.267. The method of claim 265 , wherein Ris alkylor substituted alkyl.268. The method of claim 265 , wherein Ris alkylsulfonyl claim 265 , arylsulfonyl claim 265 , aralkylsulfonyl claim 265 , heteroarylsulfonyl claim 265 , heteroaralkylsulfonyl claim 265 , or a substituted version of any of these groups.269. The method of claim 265 , wherein Ris acylor substituted acyl.270. The method of claim 269 , wherein Ris substituted acyl.272. The method of claim 271 , wherein Ris hydrogen.273. The method of claim 271 , wherein Ris alkylor substituted alkyl.274. The method of claim 271 , wherein Ris alkylsulfonyl claim 271 , arylsulfonyl claim 271 , aralkylsulfonyl claim 271 , heteroarylsulfonyl claim 271 , heteroaralkylsulfonyl claim 271 , or a substituted version of any of these groups.275. The method of claim 271 , wherein Ris acylor substituted acyl.276. The method of claim 271 , wherein Ris substituted acyl.278. The method of claim 277 , wherein the acylation agent is an acyl halide or an anhydride.279. The method of claim 277 , wherein the acylation agent is an acyl halide.280. The method of claim 277 , wherein the acylation agent is an acyl chloride.281. The method of claim 258 , wherein the modification is conducted in a medium comprising a solvent.282. The method of claim 281 , wherein the solvent is benzene or dichloromethane.283. The method of claim 258 , wherein the modification is conducted in the presence of a base.284. The method of claim 283 , wherein the base is NEt. The present application is a continuation of U.S. patent application Ser. No. 14/753,297, filed Jun. 29, 2015, now U.S. Pat. No. 9,670,147, which is a continuation of U.S. patent application Ser. No. 13/861,208, filed Apr. 11, 2013, now U.S. Pat. No. 9,102,681, which is a continuation of U.S. patent application ...

PALLADIUM-MEDIATED KETOLIZATION

Provided herein are palladium-mediated coupling reactions useful in the preparation of ketone-containing organic molecules. The provided methods can be used for the preparation of natural products and pharmaceutical agents, including Eribulin, halichondrins, and analogs thereof. The present invention also provides novel halichondrin analogs which can be prepared via the palladium-mediated coupling reactions. The novel halichondrin analogs can be used in the prevention and/or treatment of diseases or conditions (e.g., proliferative diseases such as cancer). 1111-. (canceled)114144-. (canceled)146. The compound of claim 112 , wherein Ris optionally substituted Calkyl.147. The compound of claim 146 , wherein Ris unsubstituted Calkyl.148. The compound of claim 146 , wherein Ris methyl.150153-. (canceled)154. The compound of claim 112 , wherein Ris hydrogen.155. The compound of claim 112 , wherein Ris hydrogen.156159-. (canceled)160. The compound of claim 112 , wherein Rand Rare hydrogen.161. The compound of claim 112 , wherein R claim 112 , R claim 112 , and Rare optionally substituted Calkyl.162. The compound of claim 161 , wherein R claim 161 , R claim 161 , and Rare unsubstituted Calkyl.163. The compound of claim 161 , wherein R claim 161 , R claim 161 , and Rare methyl.164. (canceled)165. A pharmaceutical composition comprising a compound of claim 112 , or a pharmaceutically acceptable salt thereof claim 112 , and optionally a pharmaceutically acceptable excipient.166. A method of inhibiting mitosis in a subject in need thereof claim 112 , the method comprising administering to the subject a compound of claim 112 , or a pharmaceutically acceptable salt thereof claim 112 , or a pharmaceutical composition thereof claim 112 , in an amount sufficient to inhibit mitosis.167. A method of triggering apoptosis in cell of a subject claim 112 , the method comprising administering to the subject a compound of claim 112 , or a pharmaceutically acceptable salt thereof claim 112 ...

NONIONIC POLYETHER SURFACTANTS

Non-ionic polyether surfactants with improved resistance to hydrolysis are provided. 2. The compound of claim 1 , wherein R is an unsubstituted C6-C50 alkyl or unsubstituted C6-C50 alkenyl.3. The compound of claim 1 , wherein R is an unsubstituted C10-C25 alkyl or unsubstituted C10-C25 alkenyl.4. The compound of claim 1 , wherein the sum of w claim 1 , x claim 1 , y claim 1 , and z is 20.6. The compound of claim 1 , wherein R is n-decyl claim 1 , n-undecyl claim 1 , n-dodecyl claim 1 , n-hexadecyl claim 1 , or n-heptadecyl.10. The method of claim 9 , wherein forming a trimethylsilyl derivative of compound of Formula (II) is done by contacting a compound of Formula (II) with a silylating agent in a suitable solvent.11. The method of claim 9 , wherein the silylating agent is hexamethyldisilazane (HMDS).12. The method of claim 9 , wherein the reducing agent is 1 claim 9 ,1 claim 9 ,3 claim 9 ,3-tetramethyldisiloxane.13. The method of claim 9 , wherein step (b) is performed at a temperature ranging from about 25° C. to about 80° C.14. The method of claim 9 , wherein step (b) does not require a solvent.15. The method of claim 9 , further comprising contacting the product of step (b) with water.16. A non-ionic polyether surfactant prepared by the method of .17. A surfactant composition comprising a compound of . This application claims the benefit of U.S. Application No. 63/053,426, filed Jul. 17, 2020, expressly incorporated herein by reference in its entirety.Polysorbates are amphiphilic, nonionic surfactants comprising fatty acid esters of polyoxyethylene sorbitan. Polysorbates are widely as research reagents and in protein pharmaceuticals to stabilize the proteins against interface-induced aggregation and to minimize surface adsorption of proteins. The main disadvantage of polysorbates is their susceptibility to hydrolysis due to the presence of an ester bond. Acid- and base-promoted hydrolytic degradation as well as enzymatic degradation of polysorbates is well- ...

Tricyclic compound and use thereof

The present invention relates to: a compound selected from the group consisting of a tricyclic compound having the structure of formula I, a pharmaceutically acceptable salt, an isomer, a solvate and a precursor thereof; and a use thereof. The compound effectively controls GPR40, and thus, can be effectively used for the prophylaxis or treatment of diseases associated with GPR40, for example, diabetes and many other diseases.

2-((2S,3S,4R,5R)-5-((S)-3-AMINO-2-HYDROXYPROP-1-YL)-4-METHOXY-3-(PHENYLSULFONYLMETHYL)TETRAHYDROFURAN-2-YL)ACETALDEHYDE DERIVATIVES AND PROCESS FOR THEIR PREPARATION

Disclosed is a compound of formula 1, as shown below, where R, R, R, R, R, Rand Rare as described herein. Also, disclosed is a process for the preparation of compounds of formula 1, and intermediates used therein. The compound of formula 1 can be useful for preparation of halichondrin analogs such as Eribulin. 3. The compound according to claim 2 , wherein Ris —CH—CH═CH claim 2 , —CH—CH═CH—CH claim 2 , —CH—CH═C(CH)or —CH—C(═O)H.47-. (canceled)8. The compound according to claim 1 , wherein one of Rand Ris H and the other is —CHSO—Ar.910-. (canceled)11. The compound according to claim 1 , wherein Ris methyl.13. The process according to claim 12 , comprising converting the primary alcohol function in the compound of formula 2 into a leaving group to form an intermediate claim 12 , followed by amination of the intermediate to form the compound of formula 1.1420-. (canceled)21. The process according to claim 12 , wherein Ris —CH—CH═CH(compound of formula 1b).23. The process according to claim 12 , wherein Ris H and Ris —CHSOAr.24. The process according to claim 12 , wherein Ris methyl.26. The process according to claim 25 , wherein the alcohol is oxidized to a ketone prior to conversion to the compound of formula 1.2737-. (canceled)39. The process according to claim 38 , wherein the conversion to form the compound of formula 3 is carried out using nucleophilic addition of an allyl silane.4041-. (canceled)4344-. (canceled)46. A process for preparation of the compound of formula 3 claim 38 , comprising the process as defined in .48. A process for preparation of the compound of formula 4 claim 42 , comprising the process as defined in .49. A process for preparation of a halichondrin analog claim 12 , comprising the process as defined in .50. (canceled) This application claims the benefit of and priority to U.S. Provisional patent application No. 61/581,164, filed Dec. 29, 2011. The content of the above-noted patent application is hereby expressly incorporated by reference ...

PROCESS FOR SYNTHESIS OF SYN AZIDO EPOXIDE AND ITS USE AS INTERMEDIATE FOR THE SYNTHESIS OF AMPRENAVIR & SAQUINAVIR

Disclosed herein is a novel route of synthesis of syn azide epoxide of formula 5, which is used as a common intermediate for asymmetric synthesis of HIV protease inhibitors such as Amprenavir, Fosamprenavir, Saquinavir and formal synthesis of Darunavir and Palinavir obtained by Cobalt-catalyzed hydrolytic kinetic resolution of racemic anti-(2SR,3SR)-3-azido-4-phenyl-1,2-epoxybutane (azido-epoxide). 2. The process according to claim 1 , wherein the allylic alcohol is aryl substituted or unsubstituted butene alcohol.3. The process according to claim 1 , wherein the Lewis acid is selected from the group consisting of BF3 claim 1 , anhyd. A1C13 claim 1 , PF5 claim 1 , TiC14 claim 1 , Ti(OiPr)4 claim 1 , zinc bromide and cerium(III) Chloride.4. The process according to claim 1 , wherein the source of azide anion is selected from inorganic azide such as sodium azide claim 1 , chlorine claim 1 , bromine claim 1 , and iodine azides or organic azide such as tosyl azide claim 1 , trimethylsilyl azide in suitable organic solvent.5. The process according to claim 1 , wherein the hydrolytic kinetic resolution is carried out in presence of (S claim 1 ,S)-Co(Salen)acetate complex in molar concentration in the range of 0.2-0.8 mol % in suitable organic solvent.6. An enantioselective synthesis of HIV protease inhibitors from syn azido epoxide of formula (+)-5 comprising converting said syn azido epoxide to said HIV protease inhibitors claim 1 , wherein said syn azido epoxide is prepared by a process comprising:i) subjecting allylic alcohol to epoxidation with m-chloroperbenzoic acid (mCPBA) to obtain racemic epoxy alcohol;ii) ring opening of epoxide with azide anion in presence of Lewis acid to produce the anti-azido alcohol, followed by selective tosylation of primary alcohol to afford tosylate;iii) treating tosylate with base to obtain racemic azido epoxide;iv) subjecting racemic azido epoxide to hydrolytic kinetic resolution to obtain corresponding 1,2-diol and syn azido epoxide ...

METHODS AND COMPOSITIONS FOR BIORENEWABLE POLYESTERS DERIVED FROM CAMPHORIC ACID

In one aspect, the disclosure relates to biorenewable polyesters and polyester copolymers derived from camphoric acid, methods of making same, and articles comprising same. The disclosed biorenewable polyesters can have a Mn of from about 5,000 Da to about 500,000 Da. Also disclosed herein is the preparation of various monomers useful in the reactions disclosed herein, e.g., cis-1,4-anhydroerythritol and bis(2-hydroxyethyl) camphorate. In various aspects, the disclosed biorenewable polyesters and polyester copolymers can be used to the production of various articles utilizing a conventional polyester or polyester copolymer, that is, to replace, in part or in whole, a conventional nonbiorenewable polyester or polyester copolymer. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure. 145-. (canceled)47. The polyester polymer of claim 46 , wherein Ris hydrogen.51. The polyester polymer of claim 46 , wherein number average molecular weight (M) is from about 7 claim 46 ,300 to about 20 claim 46 ,200 Da.52. The polyester polymer of claim 46 , wherein the dispersity is from about 2.7 to about 4.4.53. The polyester polymer of claim 46 , wherein the glass transition temperature (T) is from about −16° C. to about 125° C.54. The polyester polymer of claim 46 , wherein the temperature at which 5% mass loss under nitrogen is observed according to thermogravimetric analysis (T5) is from about 322° C. to about 368° C.55. The polyester polymer of claim 46 , wherein the polymer is non-crystalline.57. The polyester copolymer of claim 56 , wherein Ris hydrogen.62. The polyester copolymer of claim 56 , wherein the number average molecular weight (M) is from about 13 claim 56 ,300 to about 23 claim 56 ,800 Da.63. The polyester copolymer of claim 56 , wherein the dispersity is from about 2.3 to about 2.9.64. The polyester copolymer of claim 56 , wherein the glass transition temperature (T ...

PHOSPHONIC ACID CATALYST IN DEHYDRATIVE CYCLIZATION OF 5 AND 6 CARBON POLYOLS WITH IMPROVED COLOR AND PRODUCT ACCOUNTABILITY

A process for preparing materials derived from sugar alcohols such that the dehydration products exhibit better accountability and improved color to water-clear or near water-white appearance is described. In particular, the process involves employing a reducing Brønsted acid (e.g., phosphonic acid) for the catalysis of sugar alcohols to their corresponding dehydrated-cyclized products. 1. A method for preparing a cyclic dehydration product from 5 or 6 carbon polyols comprising: reacting a 5 or 6 carbon polyol with a reducing Brønsted acid catalyst in a reaction mixture , at a temperature and for a time sufficient to convert said 5 or 6 carbon polyol to corresponding cyclic dehydration products in a product mixture , wherein at least 70% of the 5 or 6 carbon polyol is converted to the corresponding cyclic dehydration products.2. The method according to claim 1 , further comprising purifying said dehydration products by at least a means selected from the group consisting of chromatography claim 1 , crystallization claim 1 , and distillation.3. The method according to claim 1 , wherein said reducing Brønsted acid catalyst is phosphonic acid.4. The method according to claim 1 , wherein said product mixture has an opacity and color appearance that ranges from translucent claim 1 , with a medium brown to light honey color claim 1 , to transparent claim 1 , clear or near water-white color after completion of said reaction time claim 1 , without being subject to a purifying or decolorizing operation.5. The method according to claim 3 , wherein said product mixture exhibits a color appearance after completion of said reaction time that is lighter and more translucent relative to a product mixture prepared using sulfuric acid catalyst at a catalyst load of ≧0.1 mol % claim 3 , instead of the phosphonic acid catalyst for the same time and temperature.6. The method according to claim 3 , wherein said product mixture exhibits reduced levels of color body formation or ...

Cyclohexenone Compositions and Process for Making Thereof

Provided herein are processes of preparing cyclohexenone compounds useful for cancer treatments and/or diseases. 120-. (canceled)221. The process of claim , wherein X is an oxygen , Y is an oxygen.231. The process of claim , wherein each of R , Rand Rindependently is H , methyl , ethyl , propyl , butyl , pentyl or hexyl.25. The process of claim 24 , wherein X is an oxygen claim 24 , Y is an oxygen.26. The process of claim 24 , wherein each of R claim 24 , Rand Rindependently is H claim 24 , methyl claim 24 , ethyl claim 24 , propyl claim 24 , butyl claim 24 , pentyl or hexyl.27. The process of claim 21 , wherein said base is a lithium salt.28. The process of claim 27 , wherein said lithium salt is n-butyllithium.29. The process of claim 24 , wherein said enolate compound is prepared under basic conditions.30. The process of claim 24 , wherein said enol compound is prepared under acidic conditions.31. The process of claim 24 , wherein Ris an acyclic or cyclic acetal claim 24 , acyclic or cylic ketal claim 24 , dithio acetal claim 24 , dithio ketal claim 24 , cyclic dithio acetal claim 24 , cyclic dithio ketal claim 24 , substituted hydrazone claim 24 , oxime claim 24 , oxime derivative claim 24 , or oxazolidine.33. The compound of claim 32 , wherein R is a hydrogen claim 32 , C(═O)CH claim 32 , C(═O)CH claim 32 , or C(═O)CH34. The compound of claim 32 , wherein each of R claim 32 , Rand Rindependently is hydrogen claim 32 , methyl claim 32 , ethyl claim 32 , propyl claim 32 , butyl claim 32 , pentyl claim 32 , hexyl claim 32 , heptyl claim 32 , or octyl optionally substituted with a aryl or heteroaryl.35. The compound of claim 34 , wherein each of R claim 34 , and Ris methyl substituted with phenyl.36. The compound of claim 32 , wherein Ris halogen claim 32 , NH claim 32 , NHCH claim 32 , N(CH) claim 32 , OCH claim 32 , OCH claim 32 , C(═O)CH claim 32 , C(═O)CH claim 32 , C(═O)OCH claim 32 , C(═O)OCH claim 32 , C(═O)NHCH claim 32 , C(═O)NHCH claim 32 , C(═O)NH claim ...

Fuels And Fuel Additives Production From Glycerol Conversion Using A Monohydric Alcohol And Heterogeneous Catalysis

The present disclosure relates to a method of converting glycerol into organic reaction products. The method may include mixing glycerol with a monohydric alcohol. The mixture of glycerol and monohydric alcohol is then reacted in the presence of a heterogeneous nano-structured catalyst, wherein the monohydric alcohol is present at subcritical/supercritical temperatures and pressures. This converts the glycerol into one or more reaction products, wherein the reaction products include an oxygenated organic reaction product. Ninety percent or greater of the glycerol is converted. 1. A method of converting glycerol , comprising:mixing glycerol containing hydroxyl groups with methanol;reacting said glycerol and methanol in the presence of a heterogeneous nano-structured catalyst, wherein said methanol is present at a temperature of 200° C. or greater and a pressure of 1,140 psia or greater;converting said glycerol into one or more reaction products, wherein one or more of said hydroxyl groups of said glycerol is converted into alkyl, alkyl ether, carbonyl, cyclic ether or alkene functionality; andwherein 90% or greater of said glycerol is converted to said reaction products containing said converted hydroxyl functionality.2. The method of claim 1 , wherein said methanol is present at a temperature in the range of 200° C. to 400° C. and a pressure in the range of 2 claim 1 ,000 psia to 3 claim 1 ,500 psia.3. The method of claim 1 , wherein said methanol is present as a supercritical fluid.4. The method of claim 1 , wherein said heterogeneous nano-structured catalyst comprises a zeolite mineral.5. The method of claim 4 , wherein said heterogenous nano-structured catalyst includes a zeolite and an oxide claim 4 , wherein said zeolite is selected from the group consisting of zeolite X and zeolite Y claim 4 , and said oxide is selected from one or more of the following: alumina claim 4 , silica and aluminosilicate.6. The method of claim 1 , wherein said heterogeneous nano- ...

Biphenyl amides with modified ether groups as hsp90 inhibitors and hsp70 inducers

Provided herein are compounds of the formulas: wherein: n, X 2 , R 3 , R 3 ′, R 4 , R 4 ′, R 5 , R 5 ′, R 6 , and R 6 ′ are as defined herein. Pharmaceutical compositions of the compounds are also provided. In some aspects, these compounds may be used for the treatment of diseases, including diabetic peripheral neuropathy or cancer.

METHOD OF MANUFACTURING DICARBOXYLIC ACIDS AND DERIVATIVES FROM COMPOSITIONS COMPRISING KETOCARBOXYLIC ACIDS

A crude composition comprising a ketocarboxylic acid such as levulinic acid, derived from biomass in an aqueous phase comprising impurities, can be efficiently converted in high yield to the corresponding dicarboxylic acid, such as succinic acid, which can be purified and dried. 2. The method of claim 1 , wherein the oxidizing agent is nitric acid and optionally a catalyst comprising vanadium pentoxide claim 1 , and optionally in the further presence of a metallic nitrite.3. The method of claim 1 , wherein the crude composition is an acidic hydrolysate of the biomass and comprises at least 5 wt. % water.4. The method of claim 1 , wherein the hydrolysate is obtained employing concentrated sulfuric acid.5. (canceled)6. The method of claim 1 , further comprising removing char particles from the crude composition prior to oxidizing the ketocarboxylic acid to the corresponding dicarboxylic acid.7. The method of claim 1 , wherein the oxidizing agent comprises nitric acid and further 0.1 to 1.0% by weight claim 1 , calculated on the basis of nitric acid claim 1 , of sodium nitrite is added.8. The method of claim 1 , wherein Ris C-Calkyl and a=1-3.9. (canceled)10. (canceled)11. The method of claim 1 , wherein the ketocarboxylic acid is obtained from a biomass conversion in the presence of an acid catalyst comprising a Brønsted-Lowry acid claim 1 , a Lewis acid claim 1 , or a combination that comprises at least one of the foregoing catalysts.12. The method of claim 1 , wherein the crude composition comprising the ketocarboxylic acid comprises at least 5 wt. % of impurities comprising biomass residue claim 1 , solid humins claim 1 , extraction solvent claim 1 , reaction by-products claim 1 , reactants claim 1 , and combinations thereof.13. (canceled)14. The method of claim 1 , wherein the impurities comprise furfural claim 1 , formic acid claim 1 , furfuryl alcohol claim 1 , hydroxymethyl furfural claim 1 , angelica lactone claim 1 , acetic acid claim 1 , methanol claim 1 , ...

INTERMEDIATES AND METHODS FOR THE SYNTHESIS OF HALICHONDRIN B ANALOGS

Methods of synthesizing intermediates useful for the synthesis of halichondrin B analogs are described. 6. The method of claim 2 , further comprising producing the compound of formula (I) by crystallizing said compound from a mixture of diastereomers under appropriate crystallization conditions.7. The method of claim 1 , further comprising producing the compound of formula (II) by crystallizing said compound from a mixture of diastereomers under appropriate crystallization conditions.10. The method of claim 8 , wherein at least one of Land Lis a protecting group selected from the group consisting of methoxymethyl claim 8 , trimethylsilyl claim 8 , triethylsilyl claim 8 , t-butyldimethylsilyl claim 8 , t-butyldiphenylsilyl claim 8 , triisopropylsilyl claim 8 , methyl claim 8 , t-butyl claim 8 , 3 claim 8 ,4-dimethoxybenzyl claim 8 , p-methoxybenzyl claim 8 , benzyl claim 8 , and trityl claim 8 , or Land Ltogether are cycloheptylidine.11. The method of claim 8 , wherein at least one of Land Lis Calkyl carbonyl claim 8 , or Land Ltogether are acetonide claim 8 , benzylidene claim 8 , pyran claim 8 , cyclohexylidene claim 8 , or cyclopentylidene.15. The method of claim 13 , wherein the divalent protecting group is a cyclohexylidine protecting group.18. The compound of claim 17 , wherein at least one of Land Lis a protecting group selected from the group consisting of methoxymethyl claim 17 , trimethylsilyl claim 17 , triethylsilyl claim 17 , t-butyldimethylsilyl claim 17 , t-butyldiphenylsilyl claim 17 , triisopropylsilyl claim 17 , methyl claim 17 , t-butyl claim 17 , 3 claim 17 ,4-dimethoxybenzyl claim 17 , p-methoxybenzyl claim 17 , benzyl claim 17 , and trityl claim 17 , or Land Ltogether are cycloheptylidine.19. The compound of claim 17 , wherein at least one of Land Lis Calkyl carbonyl claim 17 , or Land Ltogether are acetonide claim 17 , benzylidene claim 17 , cyclohexylidene claim 17 , or cyclopentylidene. This application is a continuation of U.S. application ...

NOVEL CITRIC ACID DERIVATIVE

Compounds (citric acid derivatives) represented by formulas (1) and (2) below are novel compounds having an inhibitory effect against liver disorder and can be used as liver disorder inhibitors and food additives (wherein Rrepresents a C1 to C3 alkyl group optionally having a carboxyl group or a hydroxyl group, and Rrepresents a hydrogen atom, or Rand Roptionally form a cyclic structure together to represent a C2 to C3 alkylene chain). 4. The method for inhibiting liver disorder according to claim 3 , wherein the liver disorder is nonalcoholic steatohepatitis (NASH).6. The method according to claim 3 , wherein the compound represented by formula (1) is allowed to react in an aqueous solution having a pH of 6.0 to 12.0 to which the alkaline substance for generating hydroxide ions is added claim 3 , at 80 to 130° C. for 20 minutes to 240 minutes. This application is a divisional of U.S. application Ser. No. 15/770,300 filed Apr. 23, 2018, which is a U.S. National Phase of PCT/JP2016/004789, filed on Nov. 1, 2016, which claims priority to Japanese Application No. 2015-216000, filed Nov. 2, 2015. The disclosure of each of these applications is herein incorporated by reference in its entirety.The present invention relates to a novel citric acid derivative, and more specifically, to a citric acid derivative having an inhibitory effect against liver disorder.Ume (Japanese apricot) () belongs to the subgenus of the genus of the subfamily Amygdaloideae of the family Rosaceae and is eaten in the form of processed products of ume such as pickled ume, ume wine, and ume extract (ume flesh extract). Further, ume extract has advantageous effects such as sterilization, treatment from fatigue, and stomach protection action, and thus ume extract has been taken for health. Further, ume extract is known to have an effect of improving bloodstream (see Non-patent Documents 1 and 2). It is known that the effect of improving bloodstream is derived from Mumefural which is produced by ...

COMPOSITE MATERIAL AND METHOD FOR PRODUCING THE SAME

A composite material, in particular for aeronautical applications, comprising: a first pre-impregnated layer having a resin-based matrix reinforced with fibres to give the first layer predefined mechanical properties; and a second layer of magnetic field intensifier material, superimposed on a face of the first layer and joined to the first layer along that face; the second layer comprises electrically conductive fibres, preferably of carbon, dispersed in the second layer in at least two directions with different orientations and having equivalent electrical resistivity, parallel to the aforementioned face, of less than 600 μΩm, preferably less than 200 μΩm and even more preferably less than 100 μΩm, so as to facilitate localized heating by electromagnetic induction; the first and second layers joined together define a lamina of super-weldable composite material.

Method for Preparation of 1,4-Sorbitan in Aqueous Medium

The invention discloses a method for preparation of 1,4-sorbitan by dehydration of D-sorbitol in aqueous medium, wherein one equivalent of water is removed and a cyclization occurs, followed by a treatment with ethanol and isopropanol.

STRONGLY LEWIS ACIDIC METAL-ORGANIC FRAMEWORKS FOR CONTINUOUS FLOW CATALYSIS

Lewis acidic metal-organic framework (MOF) materials comprising triflate-coordinated metal nodes are described. The materials can be used as heterogenous catalysts in a wide range of organic group transformations, including Diels-Alder reactions, epoxide-ring opening reactions, Friedel-Crafts acylation reactions and alkene hydroalkoxylation reactions. The MOFs can also be prepared with metallated organic bridging ligands to provide heterogenous catalysts for tandem reactions and/or prepared as composites with support particles for use in columns of continuous flow reactor systems. Methods of preparing and using the MOF materials and their composites are also described. 1. A method for preparing a catalyst , said method comprising:{'sub': '2', '(a) providing a parent metal-organic framework (MOF), wherein the parent MOF comprises periodic repeats of a coordination complex comprising (i) an organic bridging ligand and (ii) a metal-containing secondary building unit (SBU), wherein said metal-containing SBU comprises a metal oxo cluster comprising a metal ion M and one or more terminal or bridging OH or OHligands; and'}{'sub': '2', '(b) reacting the parent MOF with a silyl triflate to replace one or more of the one or more terminal or bridging OH or OHligands with a triflate ligand.'}2. The method of claim 1 , wherein the SBU is selected from the group consisting of Zr-oxo cluster claim 1 , a Fe-oxo cluster claim 1 , a Cr-oxo cluster claim 1 , and an A-oxo cluster.3. The method of claim 1 , wherein the organic bridging ligand is substituted with one or more carboxylate claim 1 , pyridine claim 1 , and/or phosphonate moieties.4. The method of claim 3 , wherein the organic bridging ligand is trimesic acid (BTC).5. The method of claim 1 , wherein the parent MOF is provided by contacting a parent precursor MOF with a strong acid claim 1 , wherein the parent precursor MOF comprises periodic repeats of a coordination complex comprising: (i) the organic bridging ligand and (ii ...

Method for Inhibiting Growth of Ovarian Cancer Cells

The present invention is directed to a method for inhibiting growth of ovarian cancer cells in a subject in need thereof, comprising administering to said subject a composition comprising an effective amount of 4-acetyl-antroquinonol B or a pharmaceutical acceptable salt thereof, and a pharmaceutically acceptable carrier. 1. A method for inhibiting growth of ovarian cancer cells in a subject in need thereof , comprising administering to said subject a composition comprising an effective amount of 4-acetyl-antroquinonol B or a pharmaceutical acceptable salt thereof , and a pharmaceutically acceptable carrier.2. The method of claim 1 , wherein the composition further comprises an anti-cancer drug.3. The method of claim 2 , the anti-cancer drug comprises Fluorouracil claim 2 , Oxaliplatin claim 2 , or a combination of Fluorouracil and Oxaliplatin.4. The method of claim 1 , wherein the composition has the ability of treating or preventing cancer.5Antrodia cinnamomea. The method of claim 1 , wherein the 4-acetyl-antroquinonol B is prepared through extraction of mycelium of with an organic solvent followed by purification via silica gel column chromatography.6. The method of claim 1 , wherein the effective amount of 4-acetyl-antroquinonol B is 0.01-1000 μM.7. The method of claim 1 , wherein the effective amount of 4-acetyl-antroquinonol B is 0.5-50 μM.8. The method of claim 3 , wherein the amount of Fluorouracil is 5-300 mg/mL.9. The method of claim 3 , wherein the amount of Oxaliplatin is 0.5-50 mg/mL.10. The method of claim 3 , wherein the composition prevents the subject from weight loss due to anti-cancer drug intake. The present invention claims foreign priority to Taiwanese patent application No. TW 105126636, filed on Aug. 19, 2016, which is hereby incorporated by reference in its entirety.The present invention is related to a method of treating ovarian cancer by using 4-acetyl-antroquinonol B to inhibit growth of ovarian cancer cells.Cancer, a kind of disease, can ...

Quinone based nitric oxide donating compounds

The present invention relates to nitric oxide donor compounds having a quinone based structure, to processes for their preparation and to their use in the treatment of pathological conditions where a deficit of NO plays an important role in their pathogenesis.

Methyl menthol derivative and cooling agent composition containing same

The purpose of the present invention is to provide a cooling agent composition containing a novel methyl menthol derivative having no undesirable feeling of stimulation, malodor, bitterness, or the like, it being possible to use the cooling agent composition as a cooling agent or sensory stimulation agent having exceptional persistence of a sense of coolness and refreshing feeling. The present invention pertains to a cooling agent composition containing a methyl menthol derivative represented by general formula (1A) or general formula (1B).

Method for producing hydride using unsaturated compound having carbon number of 4 as raw material

The present invention relates to a method for producing a hydride having a carbon number of 4, comprising contacting, in liquid phase, an unsaturated compound having a carbon number of 4 as a raw material with a solid catalyst obtained by loading a metal element belonging to Groups 9 to 11 of the long periodic table on a support, thereby performing hydrogenation to produce a corresponding hydride having a carbon number of 4, wherein hydrogenation is performed in the presence of, as a solvent, a 1,4-butanediol having a nitrogen component concentration of 1 ppm by weight to 1 wt % in terms of nitrogen atom.

Porous shaped metal-carbon products

The present invention provides a porous metal-containing carbon-based material that is stable at high temperatures under aqueous conditions. The porous metal-containing carbon-based materials are particularly useful in catalytic applications. Also provided, are methods for making and using porous shaped metal-carbon products prepared from these materials.

METAL OXIDE-ORGANIC HYBRID MATERIALS FOR HETEROGENEOUS CATALYSIS AND METHODS OF MAKING AND USING THEREOF

Catalysts prepared from abundant, cost effective metals, such as cobalt, nickel, chromium, manganese, iron, and copper, and containing one or more neutrally charged ligands (e.g., monodentate, bidentate, and/or polydentate ligands) and methods of making and using thereof are described herein. Exemplary ligands include, but are not limited to, phosphine ligands, nitrogen-based ligands, sulfur-based ligands, and/or arsenic-based ligands. In some embodiments, the catalyst is a cobalt-based catalyst or a nickel-based catalyst. The catalysts described herein are stable and active at neutral pH and in a wide range of buffers that are both weak and strong proton acceptors. While its activity is slightly lower than state of the art cobalt-based water oxidation catalysts under some conditions, it is capable of sustaining electrolysis at high applied potentials without a significant degradation in catalytic current. This enhanced robustness gives it an advantage in industrial and large-scale water electrolysis schemes. 1. A heterogeneous catalyst having the chemical formula{'br': None, 'sub': a', 'b', 'c', 'd', '2', 'e, 'MY(CO)O(OH)(HO)'} M is a d-block transition metal;', 'Y is a monodentate ligand, bidentate ligand, polydentate ligand, or combinations thereof;', 'a is any value from about 0 to about 3;', 'b is any value from about 0 to about 3;', 'c is any value from about 1 to about 4; and', 'd is any value from about 0 to about 4; and', 'e is any value from about 0 to about 6., 'wherein'}2. The catalyst of claim 1 , wherein M is selected from the group consisting of Cr claim 1 , Mn claim 1 , Fe claim 1 , Co claim 1 , Ni claim 1 , Cu claim 1 , Rh claim 1 , Ir claim 1 , or combinations thereof.3. The catalyst of claim 1 , wherein M is cobalt.4. The catalyst of claim 1 , wherein M is nickel.5. The catalyst of claim 1 , wherein the M is chromium.6. The catalyst of claim 1 , wherein the M is copper.7. The catalyst claim 1 , wherein the M is iron.8. The catalyst of claim 1 , ...

SYNTHETIC PROCESS FOR PREPARATION OF MACROCYCLIC C1-KETO ANALOGS OF HALICHONDRIN B AND INTERMEDIATES USEFUL THEREIN

Disclosed is a compound of formula 1, or a pharmaceutically acceptable salt thereof, where R, R, R, R, R, R, R, R, R, R, R, R, Rand Rare as disclosed herein. Also, disclosed is a process for the preparation of the compound of formula 1, or a pharmaceutically acceptable salt thereof, and intermediates used therein. The compound of formula 1 can be used in the preparation of halichondrin analogs, such as Eribulin; and a process for its preparation from the compound of formula 1 is also disclosed. 136-. (canceled)39. The compound according to claim 37 , wherein{'sup': 10', '11', '12, '(a) R, Ror Ris an alcohol protecting group, a silyl protecting group, or tert-butyldimethyl silyl (TBS); and/or'}{'sup': '13', '(b) Ris ═O; and/or'}{'sup': 9', '8', '8', '9, '(c) Ris I and/or Ris —C(═O)H, or Rand Rtogether form —C(═O)—.'}42. The compound according to claim 37 , wherein Ris —CHOR claim 37 , wherein Ris H or an alcohol protecting group.45. The compound according to claim 43 , wherein R′ is H and R″ is —CHSO—Ar claim 43 , wherein Ar is an aryl group.46. The compound according to claim 43 , wherein R′ is —CHC(═O)—R claim 43 , and wherein Ris H or OR claim 43 , wherein Ris H or a hydrocarbon claim 43 , the hydrocarbon optionally having one or more heteroatoms.49. The process according to claim 48 , wherein the coupling reaction is performed using a base.52. A process for preparation an analog of halichondrin claim 47 , comprising the process as defined in .53. Eribulin mesylate having a purity of more than 95% claim 47 , 96% claim 47 , 97% claim 47 , 98% or 99% claim 47 , as determined by HPLC.56. The compound according to claim 40 , wherein Ris —CHOR claim 40 , wherein Ris H or an alcohol protecting group. This application claims the benefit of and priority to U.S. Provisional Application Nos. 61/618,004 filed Mar. 30, 2012, entitled MACROCYCLIC ANALOGS AND METHODS FOR THEIR PREPARATION, and 61/647,127 filed May 15, 2012, entitled SYNTHETIC PROCESS FOR PREPARATION OF ...

Process for the preparation of (2r,3s)-2-(hydroxymethyl)-5-methoxytetrahydrofuran-3-ol and acetylated derivatives thereof, free of pyranose compounds

The invention provides methyl-2-deoxyriboside containing at most 5 wt % of methyl-2-deoxyribopyranoside, based on the combined weight of methyl-2-deoxyriboside and methyl-2-deoxyribopyranoside.

TREPROSTINIL DERIVATIVE COMPOUNDS AND METHODS OF USING SAME

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used. 181-. (canceled)83. The compound of claim 82 , wherein Ris Pand Ris H.84. The compound of claim 82 , wherein Ris H and Ris P.85. The compound of claim 82 , wherein Ris Pand Ris P.88. The compound of claim 82 , wherein each of Rto Ris H.89. The compound of claim 82 , wherein at least one of Rto Ris deuterium.90. The compound of claim 82 , wherein Z is —OH claim 82 , —OR claim 82 , —N(R)Ror P.91. The compound of claim 82 , wherein Z is P.92. The compound of claim 82 , wherein Z is —OH.93. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers or excipients.94. The pharmaceutical composition of claim 93 , which is formulated for transdermal delivery claim 93 , optionally via a patch.95. A method of treating pulmonary hypertension claim 82 , comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt thereof.96. The method of claim 95 , wherein the pulmonary hypertension is pulmonary arterial hypertension.97. The method of claim 95 , wherein the compound is administered orally claim 95 , topically or parenterally.98. The method of claim 97 , wherein the compound is administered transdermally claim 97 , optionally via a patch.99. The method of claim 95 , further comprising administering an additional therapeutic agent.100. The method of claim 99 , wherein the additional therapeutic agent is selected from the group consisting of vasoactive agents claim 99 , diuretics claim 99 , anticoagulants and cardiac glycosides. This application is ...

Crystalline derivatives of (S)-1-((2R,3R,4S,5S)-5-allyl-3-methoxy-4-(tosylmethyl)tetrahydrofuran-2-YL)-3-aminopropan-2-ol

Disclosed are salts of a compound of formula 1, as shown below, where R, R, R, R′ R, Rand Rare as described herein. Also, disclosed is a process for the preparation of the salts of the compounds of formula 1, and intermediates used therein. The salts of the compound of formula 1 can be useful for preparation of halichondrin analogs such as eribulin. 3. The compound according to claim 1 , wherein Ris CH—CH═CH claim 1 , —CH—CH═CH—CH claim 1 , or —CH—CH═C(CH).4. The compound according to claim 1 , wherein Ris —CH—CH═CH.5. The compound according to claim 1 , wherein Ris H claim 1 , a silyl group claim 1 , an acyl group or an alkoxycarbonyl group.6. The compound according to claim 1 , wherein Rand Reach independently is H claim 1 , allyl claim 1 , benzyl or a substituted benzyl group.7. The compound according to claim 1 , wherein one of Rand Ris H and the other is —CHSO—Ar.8. The compound according to claim 1 , wherein one of Rand Ris H and the other is —CHSO—Ar claim 1 , and the carbon to which they are attached has the S-configuration.9. The compound according to claim 1 , wherein Ris a Calkyl group.10. The compound according to claim 1 , wherein Ris methyl.11. The compound according to claim 1 , wherein the salt formed is a hydrochloric acid salt claim 1 , sulfuric acid salt claim 1 , citrate salt claim 1 , hydrobromic acid salt claim 1 , hydroiodic acid salt claim 1 , nitric acid salt claim 1 , bisulfate salt claim 1 , phosphoric acid salt claim 1 , isonicotinic acid salt claim 1 , acetic acid salt claim 1 , lactic acid salt claim 1 , salicic acid salt claim 1 , tartaric acid salt claim 1 , pantotenic acid salt claim 1 , ascorbic acid salt claim 1 , succinic acid salt claim 1 , maleic acid salt claim 1 , fumaric acid salt claim 1 , gluconic acid salt claim 1 , saccharinic acid salt claim 1 , formic acid salt claim 1 , benzoic acid salt claim 1 , glutaminic acid salt claim 1 , methanesulfonic acid salt (also referred to as mesylic acid salt) claim 1 , ethanesulfonic ...

Process for preparation of 3-((2s,5s)-4-methylene-5-(3-oxopropyl)tetrahydrofuran-2-yl)propanol derivatives and intermediates useful thereof

Discloses is a process for preparation of a compound of formula 7, or a derivative thereof, wherein PG 1 is an alcohol protecting group. Also, disclosed are intermediates and processes for their preparation. The compound of formula 7 can be useful in the preparation of halinchondrin analogs such as Eribulin.

Low-Toxicity Olefinic Ester Compositions and Methods of Using the Same

Compositions including certain olefinic ester compounds are generally disclosed. In some embodiments, such compositions are compositions having low toxicity, such as low aquatic toxicity. Therefore, in some embodiments, such compositions can be suitable used as solvents or as part of a solvent system for applications where low toxicity is desirable. Such uses include, but are not limited to, cleaning applications on or near waterways, use in oil or gas recovery, and the like. In some other embodiments, such compositions are treatment fluids for oil wells, and can therefore be introduced into an oil well to remove buildup and other deposits. In some embodiments, the olefinic ester compounds are derived from a natural oil or a natural oil derivative. 2. The compound of claim 1 , wherein Ris Calkenyl claim 1 , which is optionally substituted.3. The compound of claim 1 , wherein Ris —(CH)—CH═CH—CH.3. (canceled)4. The compound of claim 1 , wherein Ris —(CH)—CH═CH—CH—CH═CH claim 1 , —(CH)—CH═CH—CH—CH—CH claim 1 , or —(CH)—CH═CH.5. The compound of claim 4 , wherein Ris —(CH)—CH═CH—CH—CH═CH.6. The compound of claim 1 , wherein Ris —(CH)—CH═CH—CH—CH═CH—CH claim 1 , —(CH)—CH═CH—CH—CH—CH—CH claim 1 , or —(CH)—CH═CH—CH.7. The compound of claim 6 , wherein Ris —(CH)—CH═CH—CH—CH═CH—CH.8. The compound of claim 1 , wherein Ris —(CH)—CH═CH—CH—CH═CH—CH—CH claim 1 , —(CH)—CH═CH—(CH)—CH claim 1 , or —(CH)—CH═CH—CH—CH.9. The compound of claim 8 , wherein Ris —(CH)—CH═CH—CH—CH═CH—CH—CH.10. The compound of claim 1 , wherein Ris -G-R.11. The compound of claim 1 , wherein Ris R.12. (canceled)13. The compound of claim 10 , wherein Gis —CH— or —CH—CH.14. (canceled)15. (canceled)16. The compound of claim 11 , wherein Ris Ccycloalkyl claim 11 , which is optionally substituted.17. (canceled)18. (canceled)19. The compound of claim 16 , wherein Ris cyclopentyl claim 16 , cyclohexyl claim 16 , norbornyl claim 16 , or adamantyl.20. The compound of claim 19 , wherein Ris cyclohexyl.21. The compound ...

RelA Inhibitors for Biofilm Disruption

Pharmaceutical compositions comprising a RelA enzyme inhibitor and a bactericidal antibiotic, wherein said RelA enzyme inhibitor binds to the RelA enzyme in bacteria to reduce biofilm formation and to degrade biofilms that have been formed. The pharmaceutical compositions can be used to treat bacterial biofilm diseases. 1. A pharmaceutical composition comprising a RelA enzyme inhibitor and a bactericidal antibiotic , wherein said RelA enzyme inhibitor binds to RelA enzyme.2. The pharmaceutical composition of claim 1 , wherein the RelA enzyme inhibitor binds to the RelA enzyme with a predicted binding score which is less than or equal to −9 kcal/mole; or a predicted binding score which is less than −9.5 kcal/mole; or a predicted binding score which is −13.57 to −9.5 kcal/mole.5. The pharmaceutical composition of claim 1 , wherein the bactericidal antibiotic is selected from the group consisting of an aminoglycoside claim 1 , an aminomethylcycline claim 1 , an aminophenicol claim 1 , an ansamycin claim 1 , a β-lactam claim 1 , a carbapenem claim 1 , a dapsone claim 1 , a 2 claim 1 ,4-diaminopyrimidine claim 1 , a glycopeptide claim 1 , a glycycycline claim 1 , a ketolid claim 1 , a lincomycin claim 1 , a lincosamide claim 1 , a macrolide claim 1 , a nitrofuran claim 1 , an oxazolidinone claim 1 , a peptide claim 1 , a polymyxin claim 1 , a quinolone claim 1 , a rifabutin claim 1 , a streptogramin claim 1 , a sulfonamide claim 1 , a sulfone claim 1 , a tetracycline claim 1 , and combinations thereof.6. The pharmaceutical composition of claim 5 , wherein the bactericidal antibiotic is kanamycin claim 5 , norfloxacin claim 5 , or ampicillin.8. A method of treating a bacterial biofilm disease in a patient comprising administering to said patient an effective amount of the composition of .9. The method of claim 8 , wherein the bacterial biofilm disease is selected from chronic otitis media with effusion claim 8 , otorrhea claim 8 , chronic pharyngitis claim 8 , chronic ...

CATALYTIC CARBONYLATION CATALYSTS AND METHODS

In one aspect, the present invention provides catalysts for the carbonylation of heterocycles. The inventive catalysts feature metal-ligand complexes having cationic functional groups tethered to the ligand, wherein the tethered cationic groups are associated with anionic metal carbonyl species. The invention also provides methods of using the inventive catalysts to affect the ring opening carbonylation of epoxides. 1. A catalyst for the carbonylation of heterocycles comprising the combination of:i) one or more cationic functional moieties, where each cationic functional moiety comprises a linker and 1 to 4 cationic functional groups;ii) one or more ligands to which at least one cationic functional moiety is covalently tethered wherein the one or more ligand(s) are coordinated to one or two metal atoms; andiii) at least one anionic metal carbonyl species associated with a cation present on the metal complex.2. The catalyst of claim 1 , wherein the one or more ligands to which at least one cationic functional moiety is covalently tethered is selected from the group consisting of porphryin ligands and salen ligands.3. The catalyst of claim 2 , wherein catalyst comprises a salen or porphyrin complex of a metal selected from the group consisting of: Zn(II) claim 2 , Cu(II) claim 2 , Mn(II) claim 2 , Co(II) claim 2 , Ru(II) claim 2 , Fe(II) claim 2 , Co(II) claim 2 , Rh(II) claim 2 , Ni(II) claim 2 , Pd(II) claim 2 , Mg(II) claim 2 , Al(III) claim 2 , Cr(III) claim 2 , Cr(IV) claim 2 , Ti(IV) claim 2 , Fe(III) claim 2 , Co(III) claim 2 , Ti(III) claim 2 , In(III) claim 2 , Ga(III) claim 2 , Mn(III).4. The catalyst of claim 2 , wherein the catalyst comprises a salen or porphyrin complex of aluminum.5. The catalyst of claim 2 , wherein the catalyst comprises a salen or porphyrin complex of chromium.6. The catalyst of claim 1 , wherein the one or more cationic functional groups comprise onium salts.7. The catalyst of claim 1 , wherein the onium salts comprise at least one ...

METHOD FOR PREPARING AFATINIB AND INTERMEDIATE THEREOF

Revealed in the present invention is a method for preparing Afatinib (I): using 2-nitrile-4-[4-(N,N-dimethylamino)-I-oxo-2-buten-I-yl]amino-5-[(S)-(tetrahydrofuran-3-yl)oxy]aniline (II) and 4-fluoro-3-chloroaniline (III) as starting materials, and respectively performing a condensation and cyclization reaction with N,N-dimethylformamide dimethyl acetal (IV) to prepare Afatinib (I), wherein the method significantly reduces the manufacturing steps of Afatinib and greatly lower the costs. In addition, also provided in the present invention is a method for preparing an intermediate of Afatinib, wherein the method has a stable process, uses readily available starting materials, has a low cost, and all the reactions are classic reactions, suitable for meeting amplification requirements in the industry. 2. The method for preparing Afatinib according to claim 1 , wherein molar ratio of 2-nitrile-4-[4-(N claim 1 ,N-dimethylamino)-1-oxo-2-buten-I-yl]amino-5-[(S)-(tetrahydrofuran-3-yl)oxy]aniline (II) to N claim 1 ,N-dimethylformamide dimethyl acetal (IV) is 1:1-2.3. The method for preparing Afatinib according to claim 1 , wherein catalysts of condensation reaction are formic acid claim 1 , acetic acid claim 1 , methanesulfonic acid claim 1 , sulfuric acid or phosphoric acid.4. The method for preparing Afatinib according to claim 1 , wherein the temperature of condensation reaction is 0-150° C.5. The method for preparing Afatinib according to claim 1 , wherein the solvents of condensation reaction are toluene claim 1 , xylene claim 1 , dioxane claim 1 , 1 claim 1 ,2-dichloroethane claim 1 , dimethylsulfoxide claim 1 , or tetrahydrofuran.6. The method for preparing Afatinib according to claim 1 , wherein the solvents of cyclization reaction are formic acid claim 1 , acetic acid claim 1 , or a mixture of the two acids formed with toluene respectively.7. The method for preparing Afatinib according to claim 1 , wherein the temperature of cyclization reaction is 0-150° C.8. The ...

TREPROSTINIL DERIVATIVE COMPOUNDS AND METHODS OF USING SAME

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used. 181-. (canceled)83. The compound of claim 82 , wherein Ris H and Ris P.84. The compound of claim 82 , wherein Ris Pand Ris H.85. The compound of claim 82 , wherein Ris Pand Ris P.86. The compound of claim 82 , wherein Rand Rare each H.87. The compound of claim 82 , wherein each of Rto Ris H.88. The compound of claim 82 , wherein at least one of Rto Ris deuterium.89. A composition comprising at least one compound according to and at least one other component.90. The composition of claim 89 , which is formulated for transdermal delivery.91. The composition of claim 90 , which is formulated for transdermal delivery with a patch.92. The composition of claim 89 , further comprising at least one solvent.93. A method of treating pulmonary hypertension claim 82 , comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt claim 82 , solvate claim 82 , polymorph or enantiomer thereof.94. The method of claim 93 , wherein the pulmonary hypertension is pulmonary arterial hypertension.95. The method of claim 93 , wherein the compound is administered topically.96. The method of claim 95 , wherein the compound is administered transdermally.97. The method of claim 96 , wherein the compound is administered via a transdermal patch.98. The method of claim 93 , further comprising administering an additional therapeutic agent.99. The method of claim 98 , wherein the additional therapeutic agent is selected from the group consisting of vasoactive agents claim 98 , diuretics claim 98 , anticoagulants and cardiac glycosides. This application is a ...

Crystalline compound as semicarbazide-sensitive amine oxidase (ssao) enzyme inhibitor

A specific crystalline mesylate salt form of (3S)-Tetrahydrofuran-3-yl (4S)-4-isopropyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-5-carboxylate, and the use of the same in medicine. (Formula (I))

TREPROSTINIL DERIVATIVE COMPOUNDS AND METHODS OF USING SAME

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used. 147-. (canceled)49. The compound of claim 48 , wherein R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , and Rare H.50. The compound of claim 48 , wherein at least one of R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , R claim 48 , and Rare is deuterium.51. The compound of claim 48 , wherein Lis —O-alkylene-C(O)—.52. The compound of claim 48 , wherein Lis —O-alkylene-OC(O)—.53. The compound of claim 48 , wherein Lis a bond.54. The compound of claim 48 , wherein the alkylene group is a C-Calkylene group.55. The compound of claim 48 , wherein the alkylene group is a Calkylene group.56. (canceled)5863-. (canceled)66. A composition comprising a compound of claim 48 , or and one or more pharmaceutically acceptable excipients.67. The composition of claim 66 , which is formulated for transdermal delivery.6870-. (canceled)71. A method of treating pulmonary hypertension claim 66 , comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of claim 66 , or or a pharmaceutically acceptable salt thereof.72. The method of claim 71 , wherein the pulmonary hypertension is pulmonary arterial hypertension.73. The method of claim 71 , wherein the compound is administered transdermally. This application claims priority to U.S. provisional application 61/751,608 filed Jan. 11, 2013 ...

NON-FLUORINATED MONOMERS AND POLYMERS FOR SURFACE EFFECT COMPOSITIONS

The present invention relates to monomers and polymers of Formula (I): 2. The compound of wherein X is at least 50% bio-based derived.3. The compound of wherein X is 100% bio-based derived.7. The compound of wherein X is selected from formula (IIb).8. The compound of wherein X is selected from formula (IIc).9. A composition comprising a mixture of compounds of .14. The polymer compound of wherein X is at least 50% bio-based derived.16. The polymer compound of further comprising at least one repeat unit from an ethylenically unsaturated monomer having a functional group selected from a linear or branched hydrocarbon claim 12 , linear or branched fluorocarbon claim 12 , ether claim 12 , alcohol claim 12 , anhydride claim 12 , oxyalkylene claim 12 , ester claim 12 , formate claim 12 , carboxylic acid claim 12 , carbamate claim 12 , urea claim 12 , amine claim 12 , amide claim 12 , sulfonate claim 12 , sulfonic acid claim 12 , sulfonamide claim 12 , halide claim 12 , saturated or unsaturated cyclic hydrocarbon claim 12 , morpholine claim 12 , pyrrolidine claim 12 , piperidine claim 12 , or mixtures thereof.17. The polymer compound of further comprising at least one repeat unit from an ethylenically unsaturated monomer selected from linear or branched alkyl (meth)acrylates claim 12 , amino and diamino (meth)acrylates claim 12 , linear or branched fluoroalkyl (meth)acrylates optionally interrupted by O claim 12 , CH claim 12 , CHCH claim 12 , or SONH claim 12 , alkoxylated (meth)acrylates claim 12 , (meth)acylic acid claim 12 , vinyl or vinylidene chloride claim 12 , glycidyl (meth)acrylate claim 12 , vinyl acetate claim 12 , hydroxyalkylene (meth)acrylate claim 12 , urethane or urea (meth)acrylates claim 12 , (meth)acrylamides including N-methyloyl (meth)acrylamide claim 12 , alkoxyalkyl (meth)acrylamide claim 12 , styrene claim 12 , alpha-methylstyrene claim 12 , chloromethyl-substituted styrene claim 12 , ethylenediol di(meth)acrylate claim 12 , 2-acrylamido-2-methyl-1 ...

Anthracycline Derivatives For Treating Tumor Diseases

The invention relates to anthracycline derivative compounds for treating tumor diseases, and related methods, compositions, and kits.

Coupling agent for rubber composition and rubber composition for tire comprising the same

Disclosed are a coupling agent for a rubber composition and a rubber composition for a tire containing the same. The rubber composition according to the present disclosure contains a coupling agent that may induce interactions between a rubber as a raw material and carbon black, thereby improving dispersibility of the carbon black in the rubber composition. Thus, a tire with low rolling-resistance and excellent wear resistance may be realized.

PEGYLATED LIPIDS AND THEIR USE FOR DRUG DELIVERY

The invention provides poly(ethylene glycol)-lipid conjugates for use in drug delivery. 2. The compound of claim 1 , wherein X is —(CH)—.3. The compound of claim 1 , wherein X is —CH— and Y is —O— claim 1 , —S— claim 1 , —OC(O)— claim 1 , —C(O)O— claim 1 , —OC(O)N(R)— claim 1 , —N(R)C(O)O— claim 1 , —SC(O)N(R)— claim 1 , or —N(R)C(O)S—.4. The compound of claim 1 , wherein X is not —CH—; and Y is —(CRR)— claim 1 , —C(O)— claim 1 , —N(R)— claim 1 , —C(O)N(R)— claim 1 , —N(R)C(O)— claim 1 , —OC(O)N(R)— claim 1 , —N(R)C(O)O— claim 1 , —N(R)C(O)N(R)— claim 1 , —SC(O)N(R)— claim 1 , or —N(R)C(O)S—.5. The compound of claim 4 , wherein Zis —C(O)O— or —C(O)N(R)—.6. The compound of claim 1 , wherein X is —N(R)— claim 1 , —C(O)N(R)— claim 1 , —N(R)C(O)— claim 1 , —OC(O)N(R)— claim 1 , —N(R)C(O)O— claim 1 , —N(R)C(O)N(R)— claim 1 , —SC(O)N(R)— claim 1 , or —N(R)C(O)S—.7. The compound of claim 1 , wherein Y is —N(R)— claim 1 , —C(O)N(R)— claim 1 , —N(R)C(O)— claim 1 , —OC(O)N(R)— claim 1 , —N(R)C(O)O— claim 1 , —N(R)C(O)N(R)— claim 1 , —SC(O)N(R)— claim 1 , or —N(R)C(O)S—.8. The compound of claim 1 , wherein each A is Land each L claim 1 , independently claim 1 , is —OCHCH— claim 1 , —OCHCHCH— claim 1 , or —OCHCH(CH)—.9. The compound of claim 1 , wherein Ris alkoxy.10. The compound of claim 1 , wherein the molecular weight of the compound is between 500 g/mol and 5 claim 1 ,000 g/mol.11. The compound of claim 1 , wherein each of Rand R claim 1 , independently claim 1 , is a Cto Calkyl or a Cto Calkenyl group.12. The compound of claim 1 , wherein the variables q and s are each independently 1 claim 1 , 2 claim 1 , 3 claim 1 , or 4.13. The compound of claim 1 , wherein:{'sub': 1', '2', '12', '20', '12', '20, 'each of Rand R, independently, is a Cto Calkyl or a Cto Calkenyl group;'}{'sub': '2', 'X is —CH—, —O—, —OC(O)—, —C(O)O—, —C(O)NH—, —NHC(O)—, —OC(O)NH—, —NHC(O)O—, or —NHC(O)NH—;'}Y is —O—, —S—, —OC(O)—, —NHC(O)—, —OC(O)NH—, —NHC(O)O—, —NHC(O)NH—, or —SC(O)NH—;a is 1;{'sup': ' ...

ITACONIC ACID DERIVATIVES AND USES THEREOF INTREATING AN INFLAMMATORY DISEASE OR A DISEASE ASSOCIATED WITH AN UNDESIRABLE IMMUNE RESPONSE

The invention relates to compounds of formula (IW-1) and to their use in treating or preventing an inflammatory disease or a disease associated with an undesirable immune response: wherein R, R, Rand Rare as defined herein. 26-. (canceled)824-. (canceled)25. The compound or pharmaceutically acceptable salt and/or solvate thereof according to claim 1 , wherein Ris Ccycloalkyl.2628-. (canceled)29. The compound or pharmaceutically acceptable salt and/or solvate thereof according to claim 25 , wherein Ris cyclobutyl.3033-. (canceled)34. The compound or pharmaceutically acceptable salt and/or solvate thereof according to claim 1 , wherein Ris 4-10 membered heterocyclyl.3551-. (canceled)52. The compound or pharmaceutically acceptable salt and/or solvate thereof according to claim 1 , wherein Ris substituted by Rand/or Rwhen Ris methyl claim 1 , Ccycloalkyl claim 1 , 4-7 membered heterocyclyl claim 1 , phenyl or 5-6 membered heteroaryl.5358-. (canceled)59. The compound or pharmaceutically acceptable salt and/or solvate thereof according to claim 52 , wherein Ris Chaloalkyl.6079-. (canceled)80. The compound or pharmaceutically acceptable salt and/or solvate thereof according to claim 1 , wherein Ris Calkyl.81179-. (canceled)181. (canceled)182. The compound according to which is a compound selected from the group consisting of:1-(2-cyanoethyl) 4-octyl 2-methylenesuccinate;1-(2-(methylsulfonyl)ethyl) 4-octyl 2-methylenesuccinate;4-octyl 1-(3,3,3-trifluoropropyl) 2-methylenesuccinate;4-octyl 1-(oxetan-3-yl) 2-methylenesuccinate;4-octyl 1-(2-(2-oxopyrrolidin-1-yl)ethyl) 2-methylenesuccinate;1-(3-(dimethylamino)-3-oxopropyl) 4-octyl 2-methylenesuccinate;4-butyl 1-(2-(methylsulfonyl)ethyl) 2-methylenesuccinate;1-(2-cyanoethyl) 4-butyl 2-methylenesuccinate;1-(2-(2,5-dioxopyrrolidin-1-yl)ethyl) 4-octyl 2-methylenesuccinate;1-(2-cyanoethyl) 4-methyl 2-methylenesuccinate;1-(2-cyanoethyl) 4-hexyl 2-methylenesuccinate;4-methyl 1-(2-(methylsulfonyl)ethyl) 2-methylenesuccinate;4-octyl 1 ...

POROUS SHAPED METAL-CARBON PRODUCTS

The present invention provides a porous metal-containing carbon-based material that is stable at high temperatures under aqueous conditions. The porous metal-containing carbon-based materials are particularly useful in catalytic applications. Also provided, are methods for making and using porous shaped metal-carbon products prepared from these materials. 1. A process for preparing a porous , shaped metal-carbon product , the process comprising:mixing a carbonaceous material with water, a water-soluble organic binder, and a (first) metal precursor to form a metal-carbon mixture, wherein the metal precursor is a compound selected from the group consisting of a metal carbonate, a metal oxide, a metal hydroxide, a salt of a metal acid, a heteropoly acid, a metal carboxylate, a metal carbide, a metal chloride, a metal amine complex-containing compound, a hydrate thereof, and a mixture of any two or more thereof;shaping the metal-carbon mixture to form a green shaped metal-carbon product; andheating the green shaped metal-carbon product to a carbonization temperature to produce a carbonized, shaped metal-carbon product comprising a plurality of pores.211-. (canceled)12. The process of claim 1 , wherein the metal precursor comprises a metal that is a base metal.13. The process of claim 1 , wherein the metal precursor comprises a metal selected from the group consisting of Cu claim 1 , Pb claim 1 , Ni claim 1 , Zn claim 1 , Fe claim 1 , Mo claim 1 , Al claim 1 , Sn claim 1 , W claim 1 , Ta claim 1 , Co claim 1 , Bi claim 1 , Cd claim 1 , Ti claim 1 , Zr claim 1 , Sb claim 1 , Mn claim 1 , Be claim 1 , Cr claim 1 , Ge claim 1 , V claim 1 , Ga claim 1 , Hf claim 1 , In claim 1 , Nb claim 1 , Rh claim 1 , Tl claim 1 , Ru claim 1 , Rh claim 1 , Pd claim 1 , Ag claim 1 , Os claim 1 , Ir claim 1 , Pt claim 1 , Au claim 1 , and combinations thereof.1418-. (canceled)19. The process of claim 1 , wherein the metal precursor is water insoluble.20. (canceled)21. The process of claim 1 ...

COMPOSITIONS OF MONO-ALKYL ETHERS OF MONOANHYDRO-HEXITOLS, PRODUCTION METHODS THEREOF AND USE OF SAME

A composition of monoanhydro-hexitol monoalkyl ether isomers bearing an alkyl ether radical (OR) at C-3, C-5 or C-6 of the monoanhydro-hexitol, in which the alkyl group (R) is a linear or branched, cyclic or noncyclic hydrocarbon-based group comprising between 4 to 18 carbon atoms, the process for obtaining such a composition and the use thereof as a nonionic surfactant, emulsifier, lubricant, antimicrobial agent or dispersant. 1. A composition of monoanhydro-hexitol monoalkyl ether isomers bearing an alkyl ether radical (OR) in position C-3 , C-5 or C-6 of the monoanhydro-hexitol , in which the alkyl group (R) is a linear or branched hydrocarbon-based group comprising between 4 to 18 carbon atoms.2. The composition as claimed in claim 1 , characterized in that the monoanhydro hexitol is chosen from monoanhydro sorbitol claim 1 , monoanhydro mannitol claim 1 , monoanhydro iditol and monoanhydro galactitol and a mixture thereof.3. The composition as claimed in claim 1 , characterized in that it comprises at least 1% (w/w) of any one monoanhydro-hexitol monoalkyl ether isomers.4. The composition as claimed in claim 1 , characterized in that it comprises at least 90% (w/w) of monoanhydro-hexitol monoalkyl ether isomers.5. The composition as claimed in claim 1 , characterized in that a ratio [(3-alkyl monoanhydro-hexitol+5-alkyl monoanhydro-hexitol)/6-alkyl monoanhydro-hexitol] is between 0.02 and 2.6. A process for obtaining a composition of monoanhydro-hexitol monoalkyl ether isomers bearing an alkyl ether radical (OR) in position C-3 claim 1 , C-5 or C-6 of the monoanhydro-hexitol claim 1 , in which the alkyl group (R) comprises between 4 to 18 carbon atoms claim 1 , comprising the following steps:a) dehydration of a hexitol to obtain a monoanhydro-hexitol substrate; i. an aliphatic aldehyde reagent comprising from 4 to 18 carbon atoms, by acetalization, or', 'ii. a derivative of an aliphatic aldehyde reagent comprising from 4 to 18 carbon atoms, by trans- ...

ANTIOXIDANT INFLAMMATION MODULATORS: OLEANOLIC ACID DERIVATIVES WITH AMINO AND OTHER MODIFICATIONS AT C-17

This invention provides, but is not limited to, novel oleanolic acid derivatives having the formula: 1264-. (canceled)267. The method of claim 266 , wherein Ris hydrogen.268. The method of claim 266 , wherein Ris alkylor substituted alkyl.269. The method of claim 266 , wherein Ris arylor substituted aryl.270. The method of claim 266 , wherein Ris alkylor substituted alkyl.271. The method of claim 266 , where Rand Rare taken together and are -alkanediyl- or substituted —alkanediyl-.272. The method of claim 266 , where Rand Rare taken together and are —N═CHCH═CH—.274. The method of claim 273 , wherein Ris hydrogen.275. The method of claim 273 , wherein Ris alkylor substituted alkyl.276. The method of claim 273 , wherein Ris arylor substituted aryl.277. The method of claim 273 , wherein Ris alkylor substituted alkyl.278. The method of claim 273 , where Rand Rare taken together and are -alkanediyl- or substituted —alkanediyl-.279. The method of claim 273 , where Rand Rare taken together and are —N═CHCH═CH—.281. The method of claim 265 , wherein the modification is conducted in the absence of a solvent (i.e. neat).282. The method of claim 265 , wherein the modification is conducted in a medium comprising a solvent.283. The method of claim 282 , wherein the solvent is tetrahydrofuran claim 282 , benzene claim 282 , or dichloromethane.284. The method of claim 265 , wherein the modification is conducted in the presence of a base.285. The method of claim 284 , wherein the base is NEtor NaH. The present application is a continuation of U.S. patent application Ser. No. 15/615,393, filed Jun. 6, 2017, which is a continuation of U.S. patent application Ser. No. 14/753,297, filed Jun. 29, 2015, now U.S. Pat. No. 9,670,147, which is a continuation of U.S. patent spplication Ser. No. 13/861,208, filed Apr. 11, 2013, now U.S. Pat. No. 9,102,681, which is a continuation of U.S. patent application Ser. No. 13/356,455, filed on Jan. 23, 2012, now U.S. Pat. No. 8,440,854, which is a ...

Separations with organic molecular solids

A host material may be used for the separation of elements or compounds, wherein the host material is an organic molecular solid with suitable cavities for accommodating a guest material to be separated, and with interconnections between the cavities to allow the guest material to diffuse through the host material, and wherein said interconnections are closed for a proportion of the time or have a static pore limiting diameter which is smaller than the static dimension of the guest material. Applications include separations of rare gases, chiral molecules, and alkanes. One class of suitable host materials may be made by imine condensation.

ALKOXYLATED SORBITAN ESTERS AS CRUDE OIL EMULSION BREAKERS

Disclosed herein are alkoxylated sorbitan ester compounds and compositions useful in emulsion breaking applications relating to the production, transportation, storage, and separation of crude oil and natural gas. Also disclosed herein are methods of using the compounds and compositions as emulsion breakers, particularly in applications relating to the production, transportation, storage, and separation of crude oil and natural gas. 2. The compound of claim 1 , wherein Ris unsubstituted alkyl.3. The compound of claim 1 , wherein Ris unsubstituted alkyl selected from the group consisting of —CHCH; —(CH)CH; —(CH)CH; —(C)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)—CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; —(CH)CH; and —(CH)—CH.4. The compound of claim 1 , wherein Ris —(CH)CH.5. The compound of claim 4 , wherein R claim 4 , R claim 4 , and Rare each independently hydrogen.6. The compound of claim 1 , wherein Ris unsubstituted alkenyl.7. The compound of claim 1 , wherein Ris unsubstituted alkenyl selected from the group consisting of —(CH)CH═CHCHCH═CHCHCH═CHCHCH═CHCHCH═CH(CH)CH; —(CH)CH═CHCHCH═CHCHCH═CHCHCH═CHCHCH═CHCHCH═CHCHCH; —(CH)CH═CHCHCH═CHCHCH═CH(CH)CH; —(CH)CH═CHCHCHCH═CHCHCH═CH(CH)CH; —(CH)CH═CH(CH)CH═CHCHCH═CH(CH)CH; —(CH)CH═CHCHCH═CHCHCH═CHCHCH═CH(CH)CH; —(CH)CH═CHCHCH═CHCHCH═CHCHCH═CHCHCH═CHCHCH; —(CH)CH═CHCH═CHCH═CHCH═CHCH═CH(CH)CH; —(CH)CH═CH(CH)CH; —(CH)CH═CHCHCH═CHCHCH═CH(CH)CH; —(CH)CH═CHCHCH═CHCHCH═CHCHCH═CHCHCH; —(CH)CH═CHCHCH═CHCHCH═CHCHCH═CHCHCH═CHCHCH; —(CH)CH═CHCHCH═CHCHCH═CHCHCH═CHCHCH═CH(CH)CH; —(CH)CH═CHCHCH═CHCHCH═CHCHCH═CHCHCH═CHCHCH═CHCHCH; —(CH)CH═CHCHCH═CHCHCH═CHCHCH; —(CH)CH═CHCHCH═CHCHCH═CHCHCH═CH(CH)CH; —(CH)CH═CHCHCH═CHCHCH═CHCHCH═CHCHCH═CHCHCH; —(CH)CH═CHCH═CHCH═CH(CH)CH; —(CH)CH═CHCHCH═CHCHCH═CHCHCH═CH(CH)CH; —(CH)CH═CH(CH)CH; —(CH)CH═CH(CH)CH; —(CH)CH═CH(CH)CH; —(CH)CH═CHCH═ ...

SYNTHETIC PROCESS FOR PREPARATION OF MACROCYCLIC C1-KETO ANALOGS OF HALICHONDRIN B AND INTERMEDIATES USEFUL THEREIN INCLUDING INTERMEDIATES CONTAINING -SO2-(P-TOLYL) GROUPS

Disclosed is a compound of formula 1, or a pharmaceutically acceptable salt thereof, where R, R, R, R, R, R, R, R, R, R, R, R, Rand Rare as disclosed herein. Also, disclosed is a process for the preparation of the compound of formula 1, or a pharmaceutically acceptable salt thereof, and intermediates used therein. The compound of formula 1 can be used in the preparation of halichondrin analogs, such as Eribulin; and a process for its preparation from the compound of formula 1 is also disclosed. 131-. (canceled)34. The compound according to claim 32 , wherein R claim 32 , Ror Ris an alcohol protecting group claim 32 , or a silyl protecting group.35. The compound according to claim 34 , wherein the protecting group is tert-butyldimethyl silyl (TBS).36. The compound according to claim 32 , wherein Ris ═O.37. The compound according to claim 32 , wherein Ris I.38. The compound according to claim 32 , wherein Ris —C(═O)H.39. The compound according to claim 32 , wherein Rand Rtogether form —C(═O)—.40. The compound according to claim 32 , wherein Ris —CHOR claim 32 , wherein Ris H or an alcohol protecting group.41. The compound according to claim 40 , wherein the protecting group is tert-butyldiphenyl silyl (TBDPS).42. The compound according to claim 32 , wherein Ris H claim 32 , a silyl group claim 32 , an acyl group or an alkoxycarbonyl group.43. The compound according to claim 32 , wherein Rand Reach independently is H claim 32 , a silyl group claim 32 , an acyl group claim 32 , a sulfonyl group or an alkoxycarbonyl group claim 32 , and at least one of Rand Ris other than H.44. The compound according to claim 32 , wherein Rand one of Rand Rtogether form —C(═O)— claim 32 , and other Ror Ris H claim 32 , a silyl group claim 32 , an acyl group or an alkoxycarbonyl group.45. The compound according to claim 32 , wherein Ris Calkyl group or benzyl.50. The compound according to claim 48 , wherein R′ is H and R″ is —CHSO-(p-tolyl) claim 48 , wherein p-tolyl is —(CH)—CH claim 48 ...

Crystalline forms of nicotinoyl ribosides, modified derivatives thereof, and phosphorylated analogs thereof, and methods of preparation thereof

The present disclosure provides novel crystalline forms of nicotinoyl riboside compounds or derivatives of formula (I): wherein X − , Z 1 , Z 2 , n, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 are described herein, modified derivatives thereof, and phosphorylated analogs thereof, or salts, solvates, or prodrugs thereof, and methods of preparation thereof.

EFFICIENT AND SCALABLE SYNTHESES OF NICOTINOYL RIBOSIDES AND REDUCED NICOTINOYL RIBOSIDES, MODIFIED DERIVATIVES THEREOF, PHOSPHORYLATED ANALOGS THEREOF, ADENYLYL DINUCLEOTIDE CONJUGATES THEREOF, AND NOVEL CRYSTALLINE FORMS THEREOF

The present disclosure provides methods of making nicotinoyl riboside compounds or derivatives of formula (I): 2. The method of claim 1 , wherein the processing of step (c) is selected from the group consisting of batch processing claim 1 , liquid-assisted mixing claim 1 , milling claim 1 , grinding claim 1 , and extruding.3. The method of claim 1 , wherein the compound or derivative having formula (2) claim 1 , or salt thereof claim 1 , and the compound or derivative having formula (1) claim 1 , or salt thereof claim 1 , optionally wherein each Ris a TMS group claim 1 , is further treated with a molar equivalent of a Lewis acid in step (b).4. The method of claim 1 , wherein the compound or derivative having formula (I) claim 1 , or salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , is produced as a mixture of alpha- and beta-anomers in an anomeric ratio by % weight of from about 1.5:1 to about 1:4 alpha-anomer to beta-anomer.5. The method of claim 3 , wherein the compound or derivative having formula (I) claim 3 , or salt claim 3 , solvate claim 3 , or prodrug thereof claim 3 , is produced as the beta-anomer.6. The method of claim 1 , wherein the alpha- and beta-anomers of the compound or derivative having formula (I) claim 1 , or salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , are separately isolated.8. The method of claim 1 , further comprising the steps of:(d1) treating the compound or derivative having formula (I), or salt, solvate, or prodrug thereof, with a (3 Подробнее

PROCESS FOR THE PREPARATION OF A FRUCTOSE-RICH SOLUTION FROM A SOLID COMPOSITION COMPRISING FRUCTOSE AND GLUCOSE

A fructose-rich solution is prepared from a solid composition including fructose and glucose, in a process including i) admixing the solid composition including fructose and glucose with a selective solvent that consist for at least 80% wt of methanol to obtain a slurry of glucose-rich solids in a methanolic fructose-rich solution; and ii) separating the methanolic fructose-rich solution from the glucose-rich solids. 1. A process for the preparation of a fructose-rich solution from a solid composition comprising fructose and glucose , comprising:i) admixing the solid composition comprising fructose and glucose with a selective solvent that consist for at least 80% wt of methanol to obtain a slurry of glucose-rich solids in a methanolic fructose-rich solution; andii) separating the methanolic fructose-rich solution from the glucose-rich solids.2. The process according to claim 1 , wherein the selective solvent consists for at least 90% wt of methanol.3. The process according to claim 1 , wherein the selective solvent comprises up to 10% wt of water.4. The process according to claim 1 , wherein the methanolic fructose-rich solution is separated from the glucose-rich solids by means of one or more operations selected from the group consisting of sedimentation claim 1 , filtration claim 1 , centrifugation claim 1 , flotation and decantation.5. The process according to claim 1 , wherein the admixing of the solid composition and the selective solvent is carried out at a temperature in the range of 0 to 50° C.6. The process according to claim 1 , wherein the amount of selective solvent that is admixed with the solid composition is in the range of 0.1:1 to 10:1 claim 1 , based on the weight of selective solvent per weight of solid composition.7. The process according to claim 1 , wherein the methanolic fructose-rich solution has a fructose to glucose weight ratio in the range of 75:25 to 95:5.8. The process according to claim 1 , wherein the solid composition consists for ...

FE/CU-MEDIATED KETONE SYNTHESIS

Provided herein are methods for preparing ketone-containing organic molecules. The methods are based on novel iron/copper-mediated (“Fe/Cu-mediated”) coupling reactions. The Fe/Cu-mediated coupling reaction can be used in the preparation of complex molecules, such as halichondrins and analogs thereof. In particular, the Fe/Cu-mediated ketolization reactions described herein are useful in the preparation of intermediates en route to halichondrins. 8. The method of any one of - , wherein the step of coupling is carried out in the presence of copper and iron.9. The method of any one of - , wherein the iron source is iron (II) or iron (III).10. The method of any one of - , wherein the iron source is an iron complex.11. The method of claim 10 , wherein the iron complex is of the formula Fe(ligand).13. The method of any one of - claim 10 , wherein the iron complex is Fe(TMHD) claim 10 , Fe(DBM) claim 10 , or Fe(acac).14. The method of claim 10 , wherein the iron complex is of the formula Fe(X)(ligand) claim 10 , wherein each instance of X is independently halogen; and “ligand” is two phosphine ligands or a bisphosphine ligand.15. The method of claim 14 , wherein the iron complex is selected from the group consisting of Fe(Br)(dppb) claim 14 , Fe(Cl)(dppb) claim 14 , Fe(Br)(SciOPP) claim 14 , Fe(Cl)(SciOPP) claim 14 , FeBr(dppe) claim 14 , and FeCl(dppe).16. The method of claim 10 , wherein the iron complex is FeBr(PPh)or FeCl(PPh).17. The method of any one of - claim 10 , wherein the iron is present in a catalytic amount.18. The method of claim 17 , wherein the iron is present in from 1-20 mol %.19. The method of claim 18 , wherein the iron is present in approximately 5 mol %.20. The method of claim 18 , wherein the iron is present in approximately 10 mol %.21. The method of claim 18 , wherein the iron is present in approximately 15 mol %.22. The method of any one of - claim 18 , wherein the copper source is copper (I) or copper (II).23. The method of any one of - claim ...

PALLADIUM-MEDIATED KETOLIZATION

Provided herein are palladium-mediated coupling reactions useful in the preparation of ketone-containing organic molecules. The provided methods can be used for the preparation of natural products and pharmaceutical agents, including Eribulin, halichondrins, and analogs thereof. The present invention also provides novel halichondrin analogs which can be prepared via the palladium-mediated coupling reactions. The novel halichondrin analogs can be used in the prevention and/or treatment of diseases or conditions (e.g., proliferative diseases such as cancer). 1115-. (canceled)16. The method of claim 1 , wherein the reaction is carried out in the presence of zinc metal.17. (canceled)18. The method of claim 1 , wherein the single electron transfer initiator is a cobalt complex or a niobium complex.1931-. (canceled)32. The method of claim 1 , wherein the reaction is carried out in the presence of a chromium salt.3336-. (canceled)37. The method of claim 1 , wherein the reaction is carried out in the presence of a lithium halide salt.3892-. (canceled)94103-. (canceled)105109-. (canceled)112164-. (canceled)165. A pharmaceutical composition comprising a compound of claim 110 , or a pharmaceutically acceptable salt thereof claim 110 , and optionally a pharmaceutically acceptable excipient.166. A method of inhibiting mitosis in a subject in need thereof claim 110 , the method comprising administering to the subject a compound of claim 110 , or a pharmaceutically acceptable salt thereof.167. A method of triggering apoptosis in cell of a subject claim 110 , the method comprising administering to the subject a compound of claim 110 , or a pharmaceutically acceptable salt thereof.168. A method of treating a condition associated with aberrant cell proliferation in a subject in need thereof claim 110 , the method comprising administering to the subject a compound of claim 110 , or a pharmaceutically acceptable salt thereof. This application claims priority under 35 U.S.C. § 119(e) to ...

Compositions And Methods For Attracting Insects

Disclosed are compositions for attracting insects (e.g., harmful or troublesome insects such as blood-sucking and biting insects, ticks and mites) to an object (e.g., insect trap) or area (e.g., field, orchard). Also disclosed are methods for attracting insects involving treating (or exposing) the object or area with a composition containing compounds described herein (e.g., a pro-fragrance compound selected from the group consisting of an acetal, a ketal, hemiacetal and mixtures thereof, wherein at least one of a parent aldehyde, ketone, or alcohol of the pro-fragrance acetal or ketal is a fragrance compound), and optionally a carrier or carrier material. 1. (canceled) This application claims the benefit of U.S. Provisional Application No. 62/440,518 filed 30 Dec. 2016, which is incorporated herein by reference in its entirety.Disclosed are compositions for attracting insects (e.g., harmful or troublesome insects such as blood-sucking and biting insects, ticks and mites). Also disclosed are methods for attracting insects to an object (e.g., insect trap) or area (e.g., field, orchard), involving treating (or exposing) the object or area with a composition containing compounds described herein (e.g., a pro-fragrance compound selected from the group consisting of an acetal, a ketal, hemiacetal and mixtures thereof, wherein at least one of a parent aldehyde, ketone, or alcohol of the pro-fragrance acetal or ketal is a fragrance compound), and optionally a carrier or carrier material.The growing trend towards urban migration in the developing world has led to frequent outbreaks of vector borne diseases like Dengue fever, Yellow fever, and Chikungunya transmitted by, a container breeding species of mosquito. A major portion of vector control strategies involves the use of either adulticides or larvicides. However, there are growing concerns about the shortcomings of such routinely applied control measures.Arthropod vectors (e.g., mosquitos) show robust semiochemicals ...

METHOD FOR PREPARING ERIBULIN INTERMEDIATE

Intermediates used in the synthesis of Eribulin and methods for preparing the intermediates are described. For example, a compound of formula IV and a method for preparing the compound are described, wherein Ris a hydroxyl protecting group, preferably a (Calkyl group or aryl group)silyl group, and more preferably tert-butyldiphenylsilyl (TBDPS); and Ris a hydroxyl protecting group, preferably a benzyl group or (Calkyl group or aryl group)silyl group, and more preferably a benzyl group or tert-butyldimethylsilyl (TBS). A method for preparing Eribulin using the intermediates is also provided. The method has the advantages of moderate reaction conditions, is simple to execute and low cost, and is thus suitable for mass production. 3. (canceled)10. (canceled)13. (canceled)14. A method for preparing eribulin claim 5 , comprising preparing a compound of formula II according to the method of claim 5 , and then preparing eribulin from the compound of formula II.15. The compound of formula IV according to claim 1 , wherein Ris a (Calkyl or aryl)silyl group; and Ris benzyl or a (Calkyl or aryl)silyl group.16. The compound of formula V according to claim 1 , wherein Ris a (Calkyl or aryl)silyl group; and Ris benzyl or a (Calkyl or aryl)silyl group.17. The compound of formula IV or formula V according to claim 1 , wherein Ris tert-butyldiphenylsilyl (TBDPS); and Ris benzyl or tert-butyldimethylsilyl (TBS).18. The compound of formula VI according to claim 8 , wherein Ris a (Calkyl or aryl)silyl group; and Ris benzyl or a (Calkyl or aryl)silyl group.19. The compound of formula VII according to claim 8 , wherein Ris a (Calkyl or aryl)silyl group; and Ris benzyl or a (Calkyl or aryl)silyl group.20. The compound of formula VI or formula VII according to claim 8 , wherein Ris a tert-butyldiphenylsilyl (TBDPS); and Ris benzyl or tert-butyldimethylsilyl (TBS).21. The method according to claim 12 , wherein Ris tert-butyldiphenylsilyl (TBDPS); and Ris benzyl. The present invention ...

Hamamelitannin analogues and uses thereof

The present invention relates to hamamelitannin analogues, pharmaceutical compositions comprising the same, and combinations thereof with anti-microbial agents such as antibiotics or disinfectants. It in particular relates to the use of the compounds, compositions and combinations according to this invention in human or veterinary medicine, more in particular for use in the prevention and/or treatment of bacterial infections, such as Staphylococcus aureus infections, in humans or animals.

DIHYDROOROTIC ACID DEHYDROGENASE INHIBITOR

The present invention provides a novel dihydroorotic acid dehydrogenase inhibitor which is applicable to various diseases. When used as an active ingredient, a compound represented by formula (I): 2. The dihydroorotic acid dehydrogenase inhibitor according to claim 1 , whereinX represents a chlorine atom,{'sup': '2', 'Rrepresents a methyl group, and'}{'sup': 4', '0', '0, 'sub': 2', '3', '3', '3', '3', '2', '3', '2', '3', '3', '2', '3', '3', '3', '3', '3', '3', '3, 'Rrepresents —CH—CH═C(CH)—R(wherein Rrepresents an alkyl group containing 1 to 12 carbon atoms which may have a substituent on the terminal carbon and/or on a non-terminal carbon, or an alkenyl group containing 2 to 12 carbon atoms which may have a substituent on the terminal carbon and/or on a non-terminal carbon), provided that when Ro has a substituent, the substituent is selected from the group consisting of —O—CO—C(CH), —O—CO—CH(CH), —C(CH)—O—CH, —O-(2-furyl), —OH, —CH(OCH)—CH—CO—C(CH), —CHO, —CO—O—CH, —CO—CH, —O—CO—CHand —CO—C(CH).'}4. The dihydroorotic acid dehydrogenase inhibitor according to claim 1 , which comprises glycerol.5. The dihydroorotic acid dehydrogenase inhibitor according to claim 1 , which is used as an immunosuppressive agent.6. The dihydroorotic acid dehydrogenase inhibitor according to claim 1 , which is used as a therapeutic agent for rheumatism.7. The dihydroorotic acid dehydrogenase inhibitor according to claim 1 , which is used as an anticancer agent.8. The dihydroorotic acid dehydrogenase inhibitor according to claim 1 , which is used as a therapeutic agent for graft rejection in organ transplantation.9. The dihydroorotic acid dehydrogenase inhibitor according claim 1 , which is used as a therapeutic agent for diabetes.10. The dihydroorotic acid dehydrogenase inhibitor according to claim 1 , which is used as an antiviral agent.11H. pylori. The dihydroorotic acid dehydrogenase inhibitor according to claim 1 , which is used as an anti-agent.13. The kit according to claim 12 , ...

TREPROSTINIL DERIVATIVE COMPOUNDS AND METHODS OF USING SAME

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used. 2. The compound of claim 1 , wherein Ris Pand Ris H.3. The compound of claim 1 , wherein Ris H and Ris P.4. The compound of claim 1 , wherein Ris Pand Ris P.615-. (canceled)16. The compound of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare H claim 1 , or wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare deuterium.17. (canceled)18. The compound of claim 1 , wherein Z is —OR claim 1 , —N(R)R claim 1 , or P.19. (canceled)20. The compound of claim 1 , wherein Z is —OH claim 1 , —OR claim 1 , —N(R)R claim 1 , or P.21. (canceled)22. The compound of claim 1 , wherein Z is not —OH and Ris not unsubstituted or substituted benzyl.25. The compound of claim 24 , wherein Z is —OR.26. The compound of claim 24 , wherein Z is —N(R)R.27. The compound of claim 24 , wherein Z is —SR.28. The compound of claim 24 , wherein Z is P.29. The compound of claim 24 , wherein Z is ORand Ris bicycloalkyl claim 24 , alkylcycloalkyl claim 24 , or alkylcycloheteroalkyl.30. The compound of claim 24 , wherein Ris haloalkyl.31. (canceled)32. The compound of claim 24 , wherein Ris hydrogen and Ris P.33. The compound of claim 24 , wherein Ris Pand Ris hydrogen.34. The compound of claim 24 , wherein Ris Pand Ris P.35. The compound of claim 24 , wherein Rand Rare each hydrogen.36. A compound according to claim ...

TREPROSTINIL DERIVATIVE COMPOUNDS AND METHODS OF USING SAME

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used. 157-. (canceled)60. The compound of claim 58 , wherein R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , and Rare H.61. The compound of claim 58 , wherein at least one of R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , R claim 58 , and Ris deuterium.62. (canceled)64. (canceled)65. (canceled)66. A composition comprising a compound of or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers or excipients.67. The composition of claim 66 , which is formulated for transdermal delivery.68. The composition of claim 66 , which is formulated for transdermal delivery with a patch.6972-. (canceled)73. A method of treating pulmonary hypertension claim 58 , comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt thereof.74. (canceled)75. (canceled)76. The method of claim 73 , wherein the compound is administered orally claim 73 , topically or parenterally.77. The method of claim 76 , wherein the compound is administered transdermally.78. The method of claim 73 , wherein the pulmonary hypertension is pulmonary arterial hypertension.79. The method of claim 73 , further comprising administering an additional therapeutic agent.80. The method of claim 79 , wherein the additional therapeutic agent is ...

TREPROSTINIL DERIVATIVE COMPOUNDS AND METHODS OF USING SAME

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used.

PROCESS FOR THE PREPARATION OF ALISKIREN

The present invention provides a novel process and novel intermediates useful in the synthesis of pharmaceutically active compounds, especially renin inhibitors, such as Aliskiren, or a salt thereof, preferably Aliskiren hemifumarate.

Novel process for preparing polyol glycosides

A process for preparing a composition (C 1 ) represented by the formula (I): HO—CH 2 —(CHOH) n —CH 2 —O-(G) x -H, in which G represents the remainder of a reducing sugar, n is an integer equal to 2, 3 or 4 and x, which indicates the mean degree of polymerization of the remainder G, represents a decimal number greater than 1 and less than or equal to 5, characterized in that the process includes at least one step a) of reacting a polyol of formula (A 1 ): HO—CH 2 —(CHOH) n —CH 2 —OH, in which n is an integer equal to 2, 3 or 4, with a reducing sugar of formula (II): HO-G-H, in which G represents the remainder of a reducing sugar, in the presence of an acid catalyst (C a ), and in that the acid catalyst (C a ) is chosen from phosphorous acid, phosphoric acid and polyphosphoric acid.

FE/CU-MEDIATED KETONE SYNTHESIS

Provided herein are methods for preparing ketone-containing organic molecules. The methods are based on novel iron/copper-mediated (“Fe/Cu-mediated”) coupling reactions. The Fe/Cu-mediated coupling reaction can be used in the preparation of complex molecules, such as halichondrins and analogs thereof. In particular, the Fe/Cu-mediated ketolization reactions described herein are useful in the preparation of intermediates en route to halichondrins. 8. The method of any one of - , wherein the step of coupling is carried out in the presence of copper and iron.9. The method of any one of - , wherein the iron source is iron (II) or iron (III).10. The method of any one of - , wherein the iron source is an iron complex.11. The method of claim 10 , wherein the iron complex is of the formula Fe(ligand).13. The method of any one of - claim 10 , wherein the iron complex is Fe(TMHD) claim 10 , Fe(DBM) claim 10 , or Fe(acac).14. The method of claim 10 , wherein the iron complex is of the formula Fe(X)(ligand) claim 10 , wherein each instance of X is independently halogen; and “ligand” is two phosphine ligands or a bisphosphine ligand.15. The method of claim 14 , wherein the iron complex is selected from the group consisting of Fe(Br)(dppb) claim 14 , Fe(Cl)(dppb) claim 14 , Fe(Br)(SciOPP) claim 14 , Fe(Cl)(SciOPP) claim 14 , FeBr(dppe) claim 14 , and FeCl(dppe).16. The method of claim 10 , wherein the iron complex is FeBr(PPh)or FeCl(PPh).17. The method of any one of - claim 10 , wherein the iron is present in a catalytic amount.18. The method of claim 17 , wherein the iron is present in from 1-20 mol %.19. The method of claim 18 , wherein the iron is present in approximately 5 mol %.20. The method of claim 18 , wherein the iron is present in approximately 10 mol %.21. The method of claim 18 , wherein the iron is present in approximately 15 mol %.22. The method of any one of - claim 18 , wherein the copper source is copper (I) or copper (II).23. The method of any one of - claim ...

METHOD OF PRODUCING SUGAR ALCOHOL

In the present invention, a sugar alcohol can be efficiently produced from a cellulose-containing biomass by carrying out a step (1) of filtering an aqueous sugar solution, which is obtained by hydrolysis of a cellulose-containing biomass, by passing the solution through a separation membrane having a molecular cut-off of 300-800 so as to remove catalyst poisons to the non-permeate side and collecting a sugar solution from the permeate side, and a step (2) of subjecting the sugar solution obtained in step (1) to a hydrogenation reaction in the presence of a metal catalyst. 1. A method for producing a sugar alcohol from a cellulose-containing biomass as a raw material , comprising:step (1): a step of filtering a sugar aqueous solution obtained by hydrolysis of the cellulose-containing biomass, through a separation membrane having a molecular weight cut-off of 300 to 800 to remove a catalyst poison to a non-permeation side and collecting a sugar solution from a permeation side; andstep (2): a step of subjecting the sugar solution obtained in the step (1) to a hydrogenation reaction in the presence of a metal catalyst.2. The method for producing a sugar alcohol according to claim 1 , wherein the separation membrane in the step (1) is a separation membrane having a molecular weight cut-off of 300 to 500.3. The method for producing a sugar alcohol according to claim 1 , wherein the separation membrane in the step (1) is a separation membrane having a molecular weight cut-off of 600 to 800.4. The method for producing a sugar alcohol according to any one of to claim 1 , wherein the metal catalyst in the step (2) is a ruthenium catalyst or a Raney nickel catalyst.5. The method for producing a sugar alcohol according to any one of to claim 1 , wherein the sugar alcohol comprises sorbitol and/or xylitol as a main component.6. A method for producing an anhydrous sugar alcohol claim 1 , comprising a step of producing a sugar alcohol by the production method according to any one ...

Novel process for the manufacture of 3-oxo-tetrahydrofuran

This invention relates to a novel method for the preparation of 3-oxo-tetrahydrofuran comprising oxidizing 3-hydroxy-tetrahydrofuran in the presence of a catalytic amount of 2,2,6,6-tetramethyl-piperidine-N-oxyl (TEMPO) with trichloroisocyanuric acid.

GLYCITAN ESTERS OF UNSATURATED FATTY ACIDS AND THEIR PREPARATION

A method is disclosed for making an unsaturated glycitan ester by reacting intramolecular condensates of glycitols having four or more carbons with a metathesis-derived unsaturated fatty acid in the presence of an alkaline catalyst and under conditions sufficient to form the aforesaid unsaturated glycitan fatty ester. A composition is also disclosed comprising a compound of the following structure: 1. A method for preparing a glycitan ester of an unsaturated fatty acid comprising: reacting an intramolecular condensate of a glycitol having four or more carbon atoms with a metathesis-derived unsaturated fatty acid in the presence of an alkaline catalyst and under conditions sufficient to form the glycitan ester.2. (canceled)3. (canceled)4. The method of wherein the catalyst is employed in an amount up to the equivalent in the range of from about 0.01 to about 3.0 percent by weight of the unsaturated fatty ester produced.5. The method of wherein the intramolecular condensate of the glycitol is produced by intramolecular condensation in the presence of an acid catalyst under conditions sufficient to produce the intramolecular condensate of the glycitol with a hydroxyl value in the range of from about 1150 to about 1400.6. (canceled)7. (canceled)8. The method of wherein the glycitol is hexitol.9. The method of wherein the metathesis-derived unsaturated fatty acids are selected from the group consisting of 9-decenoic acid claim 1 , 9-dodecenoic acid claim 1 , 9-tridecenoic acid claim 1 , 9-pentadecenoic acid claim 1 , or 9-octadecenoic acid claim 1 , 9-octadecen-1 claim 1 ,18-dioic and ester of any thereof.10. The method of wherein the hexitol comprises sorbitol claim 8 , mannitol claim 8 , dulcitol claim 8 , or a mixture thereof.11. The method of wherein the hydroxyl groups of the unsaturated fatty ester of the intramolecular condensate of the glycitol produced are oxyalkylenated.12. The method of wherein the unsaturated fatty acid is produced by cross-metathesis of an ...

Compositions And Methods For Attracting Insects

Disclosed are compositions for attracting insects (e.g., harmful or troublesome insects such as blood-sucking and biting insects, ticks and mites) to an object (e.g., insect trap) or area (e.g., field, orchard). Also disclosed are methods for attracting insects involving treating (or exposing) the object or area with a composition containing compounds described herein (e.g., a pro-fragrance compound selected from the group consisting of an acetal, a ketal, hemiacetal and mixtures thereof, wherein at least one of a parent aldehyde, ketone, or alcohol of the pro-fragrance acetal or ketal is a fragrance compound), and optionally a carrier or carrier material. This application claims the benefit of U.S. Provisional Application No. 62/440,518 filed 30 Dec. 2016, which is incorporated herein by reference in its entirety.Disclosed are compositions for attracting insects (e.g., harmful or troublesome insects such as blood-sucking and biting insects, ticks and mites). Also disclosed are methods for attracting insects to an object (e.g., insect trap) or area (e.g., field, orchard), involving treating (or exposing) the object or area with a composition containing compounds described herein (e.g., a pro-fragrance compound selected from the group consisting of an acetal, a ketal, hemiacetal and mixtures thereof, wherein at least one of a parent aldehyde, ketone, or alcohol of the pro-fragrance acetal or ketal is a fragrance compound), and optionally a carrier or carrier material.The growing trend towards urban migration in the developing world has led to frequent outbreaks of vector borne diseases like Dengue fever, Yellow fever, and Chikungunya transmitted by, , a container breeding species of mosquito. A major portion of vector control strategies involves the use of either adulticides or larvicides. However, there are growing concerns about the shortcomings of such routinely applied control measures.Arthropod vectors (e.g., mosquitos) show robust semiochemicals induced ...

PRODUCTION OF PROTOANEMONIN BY OXIDATION OF LEVULINIC ACID OR ANGELICALACTONE ISOMERS

A process for forming protoanemonin from an amount of levulinic acid or an amount of α-Angelica lactone using oxidative dehydrogenation. Biomass-derived levulinic acid (LA) is a green platform chemical and, using an oxidative scission pathway can be transformed into cyclic intermediates, namely angelicalactones to form protoanemonin. The oxidative dehydrogenation may be heterogeneously catalyzed in a gas-phase to perform aerobic oxidation using a solid oxide such as vanadium oxide. Protoanemonin is an intriguing polyfunctional molecule that is uniquely suited to bio-based production, and can be synthesized in yields from 50%-75% during periods of transient reactor operation. 1. A process of forming protoanemonin , comprising the steps of:providing an amount of levulinic acid or an amount of α-Angelica lactone; andperforming oxidative dehydrogenation of the amount of levulinic acid or the amount of α-Angelica lactone to form an amount of protoanemonin.2. The process of claim 1 , wherein the step of oxidative dehydrogenation is heterogeneously catalyzed.3. The process of claim 1 , wherein the step of oxidative dehydrogenation is performed in a gas-phase.4. The process of claim 1 , wherein the step of oxidative dehydrogenation comprises aerobic oxidation.5. The process of claim 1 , wherein the step of oxidative dehydrogenation is performed with a solid oxide catalyst.6. The process of claim 5 , wherein the solid oxide catalyst is performed with vanadium oxide.7. The process of claim 1 , wherein the step of oxidative dehydrogenation includes the formation of β-Angelica lactone as an intermediate product.8. The process of claim 1 , wherein the step of oxidative dehydrogenation is performed at a temperature of 473 Kelvin. This application claims priority to U.S. Provisional Application No. 62/960,848, filed on Jan. 14, 2020.This invention was made with government support under Grant No. 1454346 awarded by the National Science Foundation (NSF). The government has certain ...

Fluorine-Containing Sulfonic Acid Salt, Fluorine-Containing Sulfonic Acid Salt Resin, Resist Composition, and Pattern Forming Method Using Same

Disclosed is a fluorine-containing sulfonic acid salt resin having a repeating unit represented by the following general formula (3). In the formula, each A independently represents a hydrogen atom, a fluorine atom or a trifluoromethyl group, and n represents an integer of 1-10. W represents a bivalent linking group, Rrepresents a hydrogen atom or a monovalent organic group, and M represents a monovalent cation. A resist composition containing this resin is further superior in sensitivity, resolution and reproducibility of mask pattern and is capable of forming a pattern with a low LER. 2. The fluorine-containing sulfonic acid salt resin of claim 1 , wherein the monovalent organic group Ris a Corganic group and a group containing any group of the following (a) to (g) claim 1 ,(a) an alicyclic group having a carbon ring containing an ether bond (—O—) or carbonyl group (—C(═O)—) wherein any hydrogen atom bonded to a carbon of the ring may be replaced with a hydroxy group or an acetoxy group,(b) a group having an aromatic ring in which at least one hydrogen atom has been replaced with a hydroxy group,(c) a fluoroalcohol group,(d) a group having a ring prepared by a condensation of a ring containing an ether bond (—O—), a thioether bond (—S—), an imino group (—NH—), a carbonyl group (—C(═O)—) or a thiocarbonyl group (—C(═S)—), with an aromatic ring,{'sub': '1-3', '(e) a Calkyl group,'}(f) an alicyclic group in which a hydroxy group and a fluorine atom or trifluoromethyl group have been bonded to the same carbon of the ring, and(g) an alicyclic group in which any hydrogen atom has been replaced with a cyano group-containing group, a hydroxy group, or an acetoxy group.6. The fluorine-containing sulfonic acid salt resin of claim 1 , further comprising at least one repeating unit selected from the group consisting of repeating units formed by a cleavage of a polymerizable double bond contained in an olefin claim 1 , a fluorine-containing olefin claim 1 , an acrylic acid ...

Method for Producing Bio-Based Homoserine Lactone and Bio-Based Organic Acid from O-Acyl Homoserine Produced by Microorganisms

The present invention relates to a method of producing bio-based homoserine lactone and bio-based organic acid through hydrolysis of O-acyl homoserine produced by a microorganism in the presence of an acid catalyst. According to the present invention, O-acyl homoserine produced by a microorganism is used as a raw material for producing 1,4-butanediol, gamma-butyrolactone, tetrahydrofuran and the like, which are industrially highly useful. The O-acyl homoserine produced by a microorganism can substitute conventional petrochemical products, can solve environmental concerns, including the emission of pollutants and the exhaustion of natural resources, and can be continuously renewable so as not to exhaust natural resources.

CATALYTIC CARBONYLATION CATALYSTS AND METHODS

In one aspect, the present invention provides catalysts for the carbonylation of heterocycles. The inventive catalysts feature metal-ligand complexes having cationic functional groups tethered to the ligand, wherein the tethered cationic groups are associated with anionic metal carbonyl species. The invention also provides methods of using the inventive catalysts to affect the ring opening carbonylation of epoxides. 1. A catalyst for the carbonylation of heterocycles comprising the combination of:i) one or more cationic functional moieties, where each cationic functional moiety comprises a linker and 1 to 4 cationic functional groups;ii) one or more ligands to which at least one cationic functional moiety is covalently tethered wherein the one or more ligand(s) are coordinated to one or two metal atoms; andiii) at least one anionic metal carbonyl species associated with a cation present on the metal complex.2. The catalyst of claim 1 , wherein the one or more ligands to which at least one cationic functional moiety is covalently tethered is selected from the group consisting of porphryin ligands and salen ligands.3. The catalyst of claim 2 , wherein catalyst comprises a salen or porphyrin complex of a metal selected from the group consisting of: Zn(II) claim 2 , Cu(II) claim 2 , Mn(II) claim 2 , Co(II) claim 2 , Ru(II) claim 2 , Fe(II) claim 2 , Co(II) claim 2 , Rh(II) claim 2 , Ni(II) claim 2 , Pd(II) claim 2 , Mg(II) claim 2 , ARM) claim 2 , Cr(III) claim 2 , Cr(IV) claim 2 , Ti(IV) claim 2 , Fe(III) claim 2 , Co(III) claim 2 , Ti(III) claim 2 , In(III) claim 2 , Ga(III) claim 2 , Mn(III).4. The catalyst of claim 2 , wherein the catalyst comprises a salen or porphyrin complex of aluminum.5. The catalyst of claim 2 , wherein the catalyst comprises a salen or porphyrin complex of chromium.6. The catalyst of claim 1 , wherein the one or more cationic functional groups comprise onium salts.7. The catalyst of claim 1 , wherein the onium salts comprise at least one of ...

ENANTIOSELECTIVE PROCESS FOR SYNTHESIS OF (+)- PETROMYROXOL AND ITS DIASTEREOMERS

An enantioselective process for the synthesis of (+)-petromyroxol and its Diastereomers from (3aR,5R,6aR)-2,2-dimethyl-5-((R)-oxiran-2-yl)tetrahydrofuro[2,3-d][1,3]dioxole. 1. A process for synthesis of (+)-petromyroxol or its Diastereomers from an epoxide (3aR ,5R ,6aR)-2.2-dimethyl-5-((R)-oxiran-2-yl)tetrahydrofuro[2 ,3-d]1 ,3]dioxole comprising the steps of:a) Subjecting the epoxide for ring opening using n-BuLi to afford an alcohol (S)-1-((3aR,5R,6aR)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)hexan-1-ol;b) Benzylating free —OH group of the alcohol of step (a) in the presence of NaH and benzyl bromide in THF to afford a benzylether (3aR,5R,6aR)-5-(S)-1-(benzyloxy)hexyl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole;{'sub': 3', '2, 'c) Subjecting the benzylether of step (b) for C-allylation with Allyltrimethylsilane in presence of BF.EtO in dichloromethane to afford mixture of α and β-C-allylglycosides (2R,3R,5R)-2-allyl-5-((S)-1-(benzyloxy)hexyl)tetrahydrofuran-3-ol α or (2S,3R,5R)-2-allyl-5-((S)-1-(benzyloxy)hexyl)tetrahydrofuran-3-ol β;'}d) Subjecting one or the other allylglycosides of step (c) for acetylation to afford corresponding acetates (2R,3R,5R)-2-allyl-5-((S)-1-(benzyloxy)hexyptetrahydrofuran-3-ol-α or (2S,3R,5R)-2-allyl-5-((S)-1-(benzyloxy)hexyl)tetrahydroffiran-3-ol-β, respectively;e) Subjecting compounds (2R,3R,5R)-2-allyl-5-((S)-1-(benzyloxy)hexyl)tetrahydrofuran-3-ol-α or (2S,3R,5R)-2-allyl-5-((S)-1-(benzyloxy)hexyl)tetrahydrofuran-3-ol-β of step (c) for Mitsunobu reaction using p-nitrobenzoic acid and diisopropylazodicarboxylate and triphenyl phosphine in dichloromethane to afford corresponding benzoate;{'sub': 4', '4, 'f) Subjecting benzoate of step (e) or acetates of step (d) for oxidative olefin cleavage using OsOand NaIOto afford intermediate aldehyde followed by two-carbon Wittig homologation of said aldehyde to afford corresponding unsaturated ester;'}g) Hydrogenating unsaturated ester of step (f) to afford saturated ester;h) ...

PIPERAZINE DERIVATIVE

[Problem] To provide a compound useful as an MCreceptor agonist. 2: The compound or salt thereof according to claim 1 , wherein{'sup': '1', 'sub': 1-6', '3-8, 'Rrepresents Calkyl which may be substituted, Ccycloalkyl, or an oxygen-containing saturated hetero ring,'}{'sup': '3', 'sub': 1-6', '3-8, 'Rrepresents Calkyl, Ccycloalkyl which may be substituted, or phenyl which may be substituted,'}{'sup': 4a', '9', '9, 'sub': 1-4', '2, 'Rrepresents H, Calkyl, —C(O)R, or —S(O)R,'}{'sup': '4b', 'sub': '1-6', 'Rrepresents H or Calkyl,'}{'sup': 4a', '4b', '4a', '4b, 'sub': 1-6', '1-6, 'in a case where Rrepresents H, Ralso represents H, and in a case where Rrepresents Calkyl, Ralso represents Calkyl, and'}{'sup': '9', 'sub': 1-6', '3-8, 'Rrepresents Calkyl or Ccycloalkyl.'}5: The compound or salt thereof according to claim 4 , wherein{'sup': '3', 'sub': 1-6', '3-8, 'Rrepresents Calkyl, Ccycloalkyl, or phenyl which may be substituted with one cyano group,'}{'sup': 4a', '9, 'Rrepresents —C(O)R,'}{'sup': '4b', 'Rrepresents H, and'}{'sup': '8', 'X represents CR.'}6: The compound or salt thereof according to claim 5 , wherein{'sup': '1', 'sub': '1-6', 'Rrepresents Calkyl,'}{'sup': '3', 'sub': '3-8', 'when n represents 0, Rrepresents Ccycloalkyl, and'}{'sup': '3', 'sub': '1-6', 'when n represents 1, Rrepresents Calkyl.'}7: The compound or salt thereof according to claim 6 , wherein{'sup': '1', 'Rrepresents tert-butyl,'}{'sup': 2a', '2b, 'Rand Rare the same as or different from each other and each represent H or methyl,'}{'sup': 2a', '2b, 'Rand Rdo not simultaneously represent H,'}{'sup': '3', 'when n represents 0, Rrepresents cyclohexyl,'}{'sup': '3', 'when n represents 1, Rrepresents isopropyl or tert-butyl,'}{'sup': '8', 'X represents CR,'}{'sup': '6', 'Rrepresents F or Cl,'}{'sup': '8', 'Rrepresents H or F, and'}{'sup': '9', 'Rrepresents methyl.'}8: The compound or salt thereof according to claim 1 , wherein the compound is selected from the group consisting of:N-{(1S)-2-[(3S)-4 ...

PROCESS FOR THE PRODUCTION OF HYDROCARBONS

The invention relates to a process for the production of gamma-valerolactone (GVL) by gas phase hydrogenation of furfural or furfuryl alcohol in the presence of a solid catalyst. The conversion of furfural or furfuryl alcohol to GVL is conducted in one single step. 1. Process for the production of gamma-valerolactone (GVL) by conversion in the gas phase of a stream comprising furfural or a stream comprising furfuryl alcohol in the presence of a heterogeneous catalyst , comprising copper and alumina.2. Process according to wherein the stream comprising furfural or stream comprising furfuryl alcohol is co-fed with water.3. Process according to claim 1 , wherein the copper alumina catalyst is in form of copper-alumina (Cu—Al) spinel.4. Process according to claim 3 , wherein the copper-alumina spinel is a precipitated stoichiometric Cu—Al spinel (CuAlO).5. Process according to claim 1 , wherein the catalyst is prepared by a co-precipitation method comprising the use of a Cu and Al solution.6. Process according to claim 5 , wherein the atomic ratio Cu/Alin the Cu and Al solution is in the range 1/9 to 7/3 and the co-precipitation is conducted together with a basic solution.7. Process according to claim 1 , wherein the process is conducted at a reaction temperature in the range 100 to 300° C. claim 1 , preferably 100-200° C. claim 1 , more preferably 120-190° C. claim 1 , most preferably 160-180° C.8. Process according to claim 1 , wherein the reaction pressure is in the range 1-30 atm claim 1 , preferably 10-25 atm claim 1 , more preferably 20 atm.9. Process according to claim 1 , wherein furfural is derived from C5-sugars.10. Process according to claim 1 , further comprising converting GVL to liquid hydrocarbons.11. Use of GVL produced according to claim 1 , for the production of liquid hydrocarbons.12. Use of a solid catalyst comprising copper and alumina claim 1 , for the production of gamma-valerolactone (GVL) by gas phase hydrogenation of furfural or furfuryl ...

Intermediates and methods for the synthesis of halichondrin b analogs

Methods of synthesizing intermediates useful for the synthesis of halichondrin B analogs are described.

Process for producing 1,4- butanediol by hydrogenating dialkyl maleate in mixed liquid/vapor phase

A process for the production of 1,4-butanediol and tetrahydrofuran by catalytic hydrogenation of dialkyl maleates includes the following steps: a) hydrogenating a stream of dialkyl maleate in a first stage of reaction over suitable catalysts to produce dialkyl succinate; b) further hydrogenating the dialkyl succinate in a second stage of reaction, by using a different suitable catalyst, for producing mainly 1,4-butanediol, together with gamma-butyrolactone and tetrahydrofuran as co-products. In both stages of reaction the conditions, as hydrogen/organic feed ratio, pressure and temperature, are such to maintain the reactors in mixed liquid/vapor phase.

Renewable Surfactants Derived from Sugar Alcohols

Polyol ether compounds and processes for their preparation. A representative process comprises melting a polyol, and reacting the molten polyol, a carbonyl compound, and hydrogen in the presence of a hydrogenation catalyst to provide the poly of ether. The polyol ether has surfactant properties. 1. A process comprising:melting a polyol; andreacting the molten polyol, a carbonyl compound and hydrogen in the presence of a hydrogenation catalyst.2. The process according to claim 1 , wherein a polyol ether is produced.4. The process according to claim 1 , wherein the carbonyl compound is selected from the group consisting of: hexanal claim 1 , heptanal claim 1 , cyclohexanecarbaldehyde claim 1 , octanal claim 1 , 2-ethylhexanal claim 1 , 2-propylheptanal claim 1 , nonanal claim 1 , decanal claim 1 , undecanal claim 1 , dodecanal claim 1 , 2-hexanone claim 1 , 2-heptanone claim 1 , cyclohexanone claim 1 , 2-octanone claim 1 , 2-ethylhexanone claim 1 , 2-nonanone claim 1 , 2-decanone claim 1 , 2-undecanone claim 1 , 2-dodecanone claim 1 , (Z)-2-(tetradeca-5 claim 1 ,13-dien-1-yl)malonaldehyde claim 1 , and 9-formyloctadecanoic acid.5. The process according to claim 1 , wherein the polyol is a sugar alcohol.7. The process according to claim 1 , wherein the polyol is selected from the group consisting of: sorbitol claim 1 , iditol claim 1 , dulcitol claim 1 , mannitol claim 1 , xylitol claim 1 , ribitol claim 1 , arabitol claim 1 , erythritol claim 1 , threitol claim 1 , and their isomers.8. The process according to claim 1 , wherein the polyol is selected from the group consisting of: erythritol claim 1 , threitol claim 1 , and 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-butanetetrol. This application claims priority to U.S. Provisional Patent Application No. 61/479,275 filed on Apr. 26, 2011, which is incorporated herein by reference in its entirety.This invention relates to surfactant compounds. This invention also relates to processes for making surfactant compounds by reacting ...

Method for Preparation of 1,4-Sorbitan

The invention discloses a method for preparation of 1,4-sorbitan by dehydration of D-sorbitol, wherein one equivalent of water is removed and a cyclization occurs, followed by a treatment with ethanol and isopropanol. 1. A method for preparation of 1 ,4-sorbitan with four consecutive steps STEP1 , STEP2 , STEP3 and STEP4 , wherein the reaction time TIME1-1 of DEHYDREAC is from 3 to 12 h;', 'DEHYDREAC is done at a temperature TEMP1, TEMP1 is from 95 to 130° C.,', 'DEHYDREAC is done at a pressure PRESS1 of 500 mbar or below,', 'STEP1 provides a mixture MIX1;, 'in STEP1 D-sorbitol is dehydrated in a dehydration reaction DEHYDREAC in the presence of p-toluenesulfonic acid and tetrabutylammonium bromide,'}in STEP2 ethanol is mixed with MIX1, STEP2 provides a mixture MIX2;in STEP3 isopropanol is mixed with MIX2, STEP3 provides a mixture MIX3;in STEP4 1,4-sorbitan is isolated from MIX3.2. The method according to claim 1 , whereinthe p-toluene sulfonic acid is used in form of p-toluenesulfonic acid monohydrate.3. The method according to claim 1 , whereinDEHYDREAC is done neat, that is only the three components D-sorbitol, p-toluenesulfonic acid and tetrabutylammonium bromide are used for and are charged for DEHYDREAC.4. The method according to claim 1 , whereinDEHYDREAC is done at a temperature TEMP1, TEMP1 is from 95 to 120° C.5. The method according to claim 1 , whereinthe reaction time TIME1-1 of DEHYDREAC is from 4 to 12 h.6. The method according to claim 1 , whereinDEHYDREAC is done at a pressure PRESS1 of 250 mbar or below.7. The method according to claim 1 , whereinwater is removed during DEHYDREAC.8. The method according to claim 1 , whereinSTEP2 is done at a temperature TEMP2 of from 60 to 90° C.9. The method according to claim 1 , whereinSTEP3 is done at a temperature TEMP3-1 of from 10 to 30° C.10. The method according to claim 1 , whereinafter the mixing of isopropanol, STEP3 comprises a cooling COOL3 of MIX3 to a temperature TEMP3-2 of from −5 to 5° C.11. The ...

SYNTHESIS OF NON-IONIC AMPHIPHILES FROM 1,4-ANHYDROXYLITOL

Amphipathic amine-esters derived from anhydropentitols are prepared through a short sequence of synthetic steps. The process is initiated by the esterification of an anhydropentitol with a fatty acid chloride or a lipase enzyme to form anhydropentitol fatty acid esters, preferably leaving at least one free hydroxyl. The free hydroxyl group(s) are then sulfonated, forming sulfonated anhydropentitol fatty acid esters. The sulfonyl moiety on the sulfonated anhydropentitol fatty acid esters are then subject to nucleophilic displacement by a hydrophilic moiety, illustrated by a primary amine such as AEE or AEEA. The synthetic pathway is efficient and affords modest to high yields of target amphiphilic compounds, which are useful at least as surfactants and plasticizer substitutes for petroleum derived compounds. 2) The compound of where said carbon side chain is between 8 and 30 carbons.3) The compound of wherein the esterified anhydropentitol compound is selected from the group consisting of anhydroxylitol claim 1 , anhydroarabitol and anhydroribitol.4) A method of making a monoester claim 1 , diester claim 1 , or triester fatty acid of an anhydropentitol according to comprising claim 1 , contacting an anhydropentitol compound with a fatty acid in the presence of a lipase enzyme.5Candida antarcticaMuchor mieheiThermomyces lanuginosisThermomyces lanuginosisMucor mieheiCandida ArticansThermomyces lanuginosis) The method of wherein the lipase enzyme is selected from the group consisting of Novozyme 435 (an immobilized lipase B with a permanently open active site) claim 4 , Lipozyme RM IM (a lipase immobilized with an active site covered by a moveable lid) claim 4 , Lipozyme TM IM (a lipase on porous silica with an active site covered by moveable lid) claim 4 , Lipex 100L (a mutant lipase with enhanced lipid surface absorption with an a active site covered by moveable lid and detergent stable) claim 4 , Palatase 20000 L (a lipase with an active site covered by a moveable ...

Anthracycline Derivatives For Treating Tumor Diseases

The invention relates to compounds of the general formula (I) in which Ris a hydrogen atom, a hydroxy or methoxy group, a halogen atom, or an NOgroup; Ris a hydrogen atom, a hydroxy or methoxy group, or an acyl or aroyl group; Ris hydrogen, trifluoroacetyl (C(═O)CF), or p-nitrobenzoyl (C(═O)PhNO), and in each case the wavy line represents both possible configurations of —ORrelative to the skeleton; Y is [C(═O)], [C(═N)—OH], [CH—OH], or [CH—NRR] in the two possible stereoisomer arrangements, wherein Rand Reither each represent a hydrogen atom or a hydrogen atom and a trifluoroacetyl group (TFA); X=O, S, or NR, in which R=hydrogen or a Cto Calkyl group; and Ris an unbranched or branched alkyl or heteroalkyl chain with a chain length of 1 to 19 elements, maximally 6 heteroatoms (O, N, S) being separated from one another in any combination by at least two carbon atoms. The invention further relates to, among others, methods for producing the compounds according to formula (I), to pharmaceutical compositions, to a pharmaceutical kit, and to the use thereof as a medicament for treating proliferative diseases or conditions, preferably cancer. 3. A compound as claimed in , in which X=0 and R , R , R , Rand Y are each as defined in or in which X=NR and R , R , R , R , Rand Y are each as defined in or in which X=S and R , R , R , Rand Y are each as defined in .5. A compound as claimed in claim 4 , characterized in that Rand Rare each hydrogen claim 4 , Y=[CH—NRR] where Ris hydrogen and Ris TFA claim 4 , X=0 and Ris the (CH—CH—O)— group with n=1 to 6 claim 4 , with a hydrogen atom or a Cto Calkyl group bonded to the terminal oxygen atom of the (CH—CH—O)— group.6. A compound as claimed in claim 5 , characterized in that Rand Rare each p-nitrobenzoyl.18. A pharmaceutical composition comprising one or more compounds of the formula (I) claim 5 , (Ia) and (IIIc) and optionally one or more pharmaceutically acceptable substances selected from auxiliaries claim 5 , carriers claim 5 , ...

METHOD FOR PRODUCING SUBSTITUTED N-ARYL PYRAZOLES

The present invention relates to a process for preparing compounds of the formula (I) 6: The process according to claim 1 , wherein Ris halogen-substituted C-C-alkyl or halogen-substituted C-C-alkoxy.7: The process according to claim 1 , wherein Rand Rin each case independently of one another are a substituent selected from hydrogen claim 1 , Cl claim 1 , Br claim 1 , F claim 1 , C-C-alkyl claim 1 , halogen-substituted C-C-alkyl claim 1 , C-C-alkoxy or halogen-substituted C-C-alkoxy.8: The process according to claim 1 , wherein{'sup': '1', 'sub': 1', '3, 'Ris halogen or (C-C)-alkyl,'}{'sup': '2', 'sub': 1', '4', '1', '4, 'Ris fluorine-substituted C-C-alkyl or fluorine-substituted C-C-alkoxy and'}{'sup': '3', 'sub': 1', '3', '1', '3', '1', '3', '1', '3, 'Ris halogen, C-C-alkyl or fluorine-substituted C-C-alkyl, C-C-alkoxy or fluorine-substituted C-C-alkoxy.'}9: The process according to claim 2 , wherein the base in step (2-a) is selected from hydrogencarbonates claim 2 , in particular NaHCOor KHCO claim 2 , carbonates claim 2 , in particular NaCOor KCO claim 2 , or hydroxides claim 2 , in particular NaOH or KOH.10: The process according to claim 1 , wherein the acid in step (1) is used in pure form or as an aqueous solution at concentrations from 10-99% by weight.11: The process according to claim 3 , wherein the alcohol R—OH in step (2-b) is used simultaneously as solvent and reagent.12: The process according to claim 3 , wherein the compound R—OH from step (2-b) is used as solvent for step (2-b) and step (3).13: The process according to claim 1 , wherein the said process comprises or consists of the steps (1) claim 1 , (2) claim 1 , (2-a) claim 1 , (2-b) and (3).14: The process according to claim 1 , wherein the said process comprises or consists of the steps (1) claim 1 , (2) claim 1 , (2-b) and (3).15: The process according to claim 1 , wherein the steps (1) and (2) are carried out together in a “one-pot” reaction claim 1 , wherein the diazonium salt (III) formed ...

10-a/BETA-D-ARABINOFURANOSYL-UNDECENES AS POTENTIAL ANTI-MYCOBACTERIAL AGENTS AND PROCESS FOR THE PREPARATION THEREOF

Disclosed herein is 10-α/β-D-Arabinofuranosylundecenes of general Formula (II) or pharmaceutically acceptable N salts thereof as anti-mycobacterial agents in vitro; (II) wherein R, R1 and R″ are as defined herein in the specification. The present invention also discloses a simple stereoselective synthesis 10-α/β-D-Arabinofuranosylundecenes of Formula (II) to target enzymes involved in the biosynthesis of cell wall of Mycobacterium and thus useful as inhibitors in the Mycobacterium tuberculosis drug development.

ANTIOXIDANT INFLAMMATION MODULATORS: OLEANOLIC ACID DERIVATIVES WITH AMINO AND OTHER MODIFICATIONS AT C-17

This invention provides, but is not limited to, novel oleanolic acid derivatives having the formula: 1264-. (canceled)266. The method of claim 265 , wherein the bond joining carbon 9 and carbon 11 of the compound is a double bond.267. The method of claim 265 , wherein the bond joining carbon 9 and carbon 11 of the compound is a single bond.268. The method of claim 265 , wherein said neurodegenerative disease is selected from the group consisting of Parkinson's disease claim 265 , Alzheimer's disease claim 265 , multiple sclerosis (MS) claim 265 , Huntington's disease and amyotrophic lateral sclerosis.269. The method of claim 268 , wherein said neurodegenerative disease is Alzheimer's disease.270. The method of claim 268 , wherein said neurodegenerative disease is MS.271. The method of claim 265 , wherein the compound is administered systemically.272. The method of claim 271 , wherein the compound is administered intravenously claim 271 , intra-arterially claim 271 , intramuscularly claim 271 , intraperitoneally claim 271 , subcutaneously or orally.273. The method of claim 265 , wherein the pharmaceutically effective amount is 0.1-1000 mg/kg.274. The method of claim 273 , wherein the pharmaceutically effective amount is administered in a single dose per day.275. The method of claim 273 , wherein the pharmaceutically effective amount is administered in two or more doses per day.277. The method of claim 276 , wherein the bond joining carbon 9 and carbon 11 of the compound is a double bond.278. The method of claim 276 , wherein the bond joining carbon 9 and carbon 11 of the compound is a single bond.280. The method of claim 279 , wherein the bond joining carbon 9 and carbon 11 of the compound is a double bond.281. The method of claim 279 , wherein the bond joining carbon 9 and carbon 11 of the compound is a single bond.283. The method of claim 282 , wherein the bond joining carbon 9 and carbon 11 of the compound is a double bond.284. The method of claim 282 , wherein ...

PREPARATION OF 2'-FLUORO-2'-ALKYL-SUBSTITUTED OR OTHER OPTIONALLY SUBSTITUTED RIBOFURANOSYL PYRIMIDINES AND PURINES AND THEIR DERIVATIVES

The present invention provides (i) processes for preparing a 2′-deoxy-2′-fluoro-2′-methyl-D-ribonolactone derivatives, (ii) conversion of intermediate lactones to nucleosides with potent anti-HCV activity, and their analogues, and (iii) methods to prepare the anti-HCV nucleosides containing the 2′-deoxy-2′-fluoro-2′-C-methyl-β-D-ribofuranosyl nucleosides from a preformed, preferably naturally-occurring, nucleoside. 8. The compound of claim 7 , wherein Ris H and Ris methyl. This application is a continuation of U.S. patent application Ser. No. 14/808,147, filed Jul. 24, 2015, which is a divisional of Ser. No. 13/917,173, filed Jun. 13, 2013, which is a continuation of U.S. patent application Ser. No. 11/225,425, filed Sep. 13, 2005, which claims the benefit of Provisional Patent Application Ser. No. 60/609,783, filed Sep. 14, 2004, Provisional Patent Application Ser. No. 60/610,035, filed Sep. 15, 2004, and Provisional Patent Application Ser. No. 60/666,230, filed Mar. 29, 2005. The entire contents of all of the above-mentioned applications are incorporated herein by reference.The present invention provides (i) processes for preparing a 2-deoxy-2-fluoro-2-methyl-D-ribonolactone derivatives, (ii) conversion of intermediate lactones to nucleosides with potent anti-HCV activity, and their analogues, and (iii) methods to prepare the anti-HCV nucleosides containing the 2′-deoxy-2′-fluoro-2′-C-methyl-β-D-ribofuranosyl nucleosides from a preformed, preferably naturally-occurring, nucleoside.HCV infection has reached epidemic levels worldwide, and has tragic effects on the infected patients. Presently there is no effective treatment for this infection and the only drugs available for treatment of chronic hepatitis C are various forms of alpha interferon (IFN-α), either alone or in combination with ribavirin. However, the therapeutic value of these treatments has been compromised largely due to adverse effects, which highlights the need for development of additional options ...

3-AMINOCYCLOPENTANE CARBOXAMIDE DERIVATIVES

Compounds of the formula I 2. Compounds according to in which{'sup': '4', 'Rdenotes H, F, Cl, OA′ or A′,'}and pharmaceutically acceptable salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.3. Compounds according to claim 1 , in which{'sub': '2', 'sup': '5', 'A denotes unbranched or branched alkyl with 1-10 C-atoms, wherein one or two non-adjacent CH- and/or CH-groups may be replaced by N- and/or O-atoms and 1-7 H-atoms may be replaced by R,'}and pharmaceutically acceptable salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.4. Compounds according to claim 1 , in which{'sup': 3', '1', '1', '3', '3, 'sub': 2', 'n', '2', 'p, 'Ar denotes phenyl, which is unsubstituted or mono-, di-, tri-, tetra- or pentasubstituted by O[C(R)]Het, Ar, A, CN and/or [C(R)]OR,'}and pharmaceutically acceptable salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.5. Compounds according to claim 1 , in which{'sup': '1', 'Ardenotes phenyl or naphthyl,'}and pharmaceutically acceptable salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.6. Compounds according to claim 1 , in which{'sup': 3', '3', '1, 'sub': 2', 'n', 'n', '2', '2, 'Het denotes a mono- or bicyclic aromatic heterocycle having 1 to 4 N, O and/or S atoms, which is unsubstituted or mono- or disubstituted by Hal, A, [C(R)]OA′, S(O)A, CN, SON(R)and/or COHet,'}and pharmaceutically acceptable salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.7. Compounds according to claim 1 , in which{'sup': '1', 'Hetdenotes a monocyclic saturated heterocycle having 1 to 4 N, O and/or S atoms, which is unsubstituted or mono- or disubstituted by A,'}and pharmaceutically acceptable salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.8. Compounds according to claim 1 , in which{'sup': 3', '3', '1, 'sub': 2', 'n', 'n', '2', '2, 'Het denotes furyl, thienyl, ...

CATALYTIC CARBONYLATION CATALYSTS AND METHODS

In one aspect, the present invention provides catalysts for the carbonylation of heterocycles. The inventive catalysts feature metal-ligand complexes having cationic functional groups tethered to the ligand, wherein the tethered cationic groups are associated with anionic metal carbonyl species. The invention also provides methods of using the inventive catalysts to affect the ring opening carbonylation of epoxides. 126-. (canceled)28. (canceled)29. The catalyst of claim 27 , wherein Mand Mare independently selected from the group consisting of Zn(II) claim 27 , Cu(II) claim 27 , Mn(II) claim 27 , Co(II) claim 27 , Ru(II) claim 27 , Fe(II) claim 27 , Rh(II) claim 27 , Ni(II) claim 27 , Pd(II) claim 27 , Mg(II) claim 27 , Al(III) claim 27 , Cr(III) claim 27 , Cr(IV) claim 27 , Ti(IV) claim 27 , Fe(III) claim 27 , Co(III) claim 27 , Ti(III) claim 27 , In(III) claim 27 , Ga(III) claim 27 , and Mn(III).30. The catalyst of claim 27 , wherein Mand Mare aluminum.31. The catalyst of claim 27 , wherein Mand Mare chromium.32. The catalyst of claim 27 , wherein Z comprises an atom selected from the group consisting of nitrogen claim 27 , phosphorous claim 27 , arsenic claim 27 , and sulfur.34. The catalyst of claim 27 , wherein the linker comprises 1-30 atoms including at least one carbon atom and optionally one or more atoms selected from the group consisting of N claim 27 , O claim 27 , S claim 27 , Si claim 27 , B claim 27 , and P.36. The catalyst of claim 27 , wherein the at least one anionic metal carbonyl species is a compound of formula: [QM′(CO)] claim 27 , wherein:Q is a ligand and need not be present,M′ is a metal atom,d is an integer between 0 and 8 inclusive,e is an integer between 1 and 6 inclusive,w is a number such as to provide a stable anionic metal carbonyl complex, andy is the charge of the anionic metal carbonyl species.37. The catalyst of claim 36 , wherein Q is a phosphine ligand or a cyclopentadienyl (cp) ligand.38. The catalyst of claim 27 , wherein the ...

EFFICIENT AND SCALABLE SYNTHESES OF NICOTINOYL RIBOSIDES AND REDUCED NICOTINOYL RIBOSIDES, MODIFIED DERIVATIVES THEREOF, PHOSPHORYLATED ANALOGS THEREOF, ADENYLYL DINUCLEOTIDE CONJUGATES THEREOF, AND NOVEL CRYSTALLINE FORMS THEREOF

The present disclosure provides methods of making nicotinoyl riboside compounds or derivatives of formula (I): 2. The method of claim 1 , wherein the processing of step (c) is selected from the group consisting of batch processing claim 1 , liquid-assisted mixing claim 1 , milling claim 1 , grinding claim 1 , and extruding.3. The method of claim 1 , wherein the compound or derivative having formula (2) claim 1 , or salt thereof claim 1 , and the compound or derivative having formula (1) claim 1 , or salt thereof claim 1 , optionally wherein each Ris a TMS group claim 1 , is further treated with a molar equivalent of a Lewis acid in step (b).4. The method of claim 1 , wherein the compound or derivative having formula (I) claim 1 , or salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , is produced as a mixture of alpha- and beta-anomers in an anomeric ratio by % weight of from about 1.5:1 to about 1:4 alpha-anomer to beta-anomer.5. The method of claim 3 , wherein the compound or derivative having formula (I) claim 3 , or salt claim 3 , solvate claim 3 , or prodrug thereof claim 3 , is produced as the beta-anomer.6. The method of claim 1 , wherein the alpha- and beta-anomers of the compound or derivative having formula (I) claim 1 , or salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , are separately isolated.8. The method of claim 1 , further comprising the steps of:(d1) treating the compound or derivative having formula (I), or salt, solvate, or prodrug thereof, with a (3 Подробнее