Processes for the preparation of dehydroepiandrosterone and its intermediates

The present application relates to a regioselective and stereoselective processes for the preparation of dehydroepi-androsterone (DHEA) and processes for its intermediates.

ENGINEERED PANTOTHENATE KINASE VARIANT ENZYMES

The present invention provides engineered pantothenate kinase (PanK) enzymes, polypeptides having PanK activity, and polynucleotides encoding these enzymes, as well as vectors and host cells comprising these polynucleotides and polypeptides. Methods for producing PanK enzymes are also provided. The present invention further provides compositions comprising the PanK enzymes and methods of using the engineered PanK enzymes. The present invention finds particular use in the production of pharmaceutical compounds. 1. An engineered pantothenate kinase comprising a polypeptide sequence having at least 85% , 86% , 87% , 88% , 89% , 90% , 91% , 92% , 93% , 94% , 95% , 96% , 97% , 98% , 99% , or more sequence identity to SEQ ID NO: 2 , SEQ ID NO: 30 , SEQ ID NO: 60 , SEQ ID NO: 132 , SEQ ID NO: 222 , SEQ ID NO: 230 , SEQ ID NO: 240 , and/or SEQ ID NO: 276 , or a functional fragment thereof.2. The engineered pantothenate kinase of claim 1 , wherein said engineered pantothenate kinase comprises a polypeptide sequence having at least 85% claim 1 , 86% claim 1 , 87% claim 1 , 88% claim 1 , 89% claim 1 , 90% claim 1 , 91% claim 1 , 92% claim 1 , 93% claim 1 , 94% claim 1 , 95% claim 1 , 96% claim 1 , 97% claim 1 , 98% claim 1 , 99% claim 1 , or more sequence identity to SEQ ID NO: 2 claim 1 , or a functional fragment thereof claim 1 , and wherein said engineered pantothenate kinase comprises at least one substitution or substitution set at one or more positions selected from 277/281 claim 1 , 54/240/277/281 claim 1 , 240 claim 1 , 240/277 claim 1 , 240/277/281 claim 1 , 240/277/281/282 claim 1 , 240/281 claim 1 , and 240/281/282 claim 1 , 277 claim 1 , and wherein the amino acid positions of said polypeptide sequence are numbered with reference to SEQ ID NO: 2.3. The engineered pantothenate kinase of claim 1 , wherein said engineered pantothenate kinase comprises a polypeptide sequence having at least 85% claim 1 , 86% claim 1 , 87% claim 1 , 88% claim 1 , 89% claim 1 , 90% claim ...

ENGINEERED DEOXYRIBOSE-PHOSPHATE ALDOLASES

The present invention provides engineered deoxyribose-phosphate aldolase polypeptides useful under industrial process conditions for the production of pharmaceutical and fine chemical compounds. 1. An engineered deoxyribose-phosphate aldolase comprising a polypeptide sequence having at least 85% , 86% , 87% , 88% , 89% , 90% , 91% , 92% , 93% , 94% , 95% , 96% , 97% , 98% , 99% , or more sequence identity to SEQ ID NOS: 2 , 6 , and/or 466 , or a functional fragment thereof , wherein said engineered deoxyribose-phosphate aldolase comprises at least one substitution or substitution set in said polypeptide sequence , and wherein the amino acid positions of said polypeptide sequence are numbered with reference to SEQ ID NO: 2 , 6 , and/or 466.2. The engineered deoxyribose-phosphate aldolase of claim 1 , wherein said polypeptide sequence has at least 85% claim 1 , 86% claim 1 , 87% claim 1 , 88% claim 1 , 89% claim 1 , 90% claim 1 , 91% claim 1 , 92% claim 1 , 93% claim 1 , 94% claim 1 , 95% claim 1 , 96% claim 1 , 97% claim 1 , 98% claim 1 , 99% claim 1 , or more sequence identity to SEQ ID NO:2 claim 1 , wherein said engineered deoxyribose-phosphate aldolase comprises at least one substitution or substitution set in said polypeptide sequence at one or more positions selected from 10/47/66/141/145/156 claim 1 , 2 claim 1 , 6 claim 1 , 9 claim 1 , 10/47/88/156 claim 1 , 13 claim 1 , 31 claim 1 , 46 claim 1 , 47 claim 1 , 47/134/141/212 claim 1 , 66 claim 1 , 66/88/112/134/141/143/145/212 claim 1 , 71 claim 1 , 72 claim 1 , 88 claim 1 , 94 claim 1 , 102 claim 1 , 104 claim 1 , 112 claim 1 , 116 claim 1 , 133 claim 1 , 133/173/204/235/236 claim 1 , 134 claim 1 , 145 claim 1 , 145/173 claim 1 , 147 claim 1 , 173 claim 1 , 184 claim 1 , 189 claim 1 , 197 claim 1 , 203 claim 1 , 204 claim 1 , 207 claim 1 , 226 claim 1 , 235 claim 1 , 235/236 claim 1 , and 236 claim 1 , and wherein the amino acid positions of said polypeptide sequence are numbered with reference to SEQ ID NO: ...

ENGINEERED GALACTOSE OXIDASE VARIANT ENZYMES

The present invention provides engineered galactose oxidase (GOase) enzymes, polypeptides having GOase activity, and polynucleotides encoding these enzymes, as well as vectors and host cells comprising these polynucleotides and polypeptides. Methods for producing GOase enzymes are also provided. The present invention further provides compositions comprising the GOase enzymes and methods of using the engineered GOase enzymes. The present invention finds particular use in the production of pharmaceutical and other compounds. 1. An engineered galactose oxidase comprising a polypeptide sequence having at least 85% , 86% , 87% , 88% , 89% , 90% , 91% , 92% , 93% , 94% , 95% , 96% , 97% , 98% , 99% , or more sequence identity to SEQ ID NO: 2 , 4 , 166 , 272 , 928 , 932 , 1264 , 1416 , 1598 , 1866 , 1912 , 2080 , 2300 , and/or 2424 , or a functional fragment thereof , wherein said engineered galactose oxidase comprises at least one substitution or substitution set in said polypeptide sequence , and wherein the amino acid positions of said polypeptide sequence are numbered with reference to SEQ ID NO: 2 , 4 , 166 , 272 , 928 , 932 , 1264 , 1416 , 1598 , 1866 , 1912 , 2080 , 2300 , and/or 2424.2. The engineered galactose oxidase of claim 1 , wherein said polypeptide sequence has at least 85% claim 1 , 86% claim 1 , 87% claim 1 , 88% claim 1 , 89% claim 1 , 90% claim 1 , 91% claim 1 , 92% claim 1 , 93% claim 1 , 94% claim 1 , 95% claim 1 , 96% claim 1 , 97% claim 1 , 98% claim 1 , 99% claim 1 , or more sequence identity to SEQ ID NO: 2 claim 1 , and wherein said engineered galactose oxidase comprises at least one substitution or substitution set at one or more positions in said polypeptide sequence selected from 331/406/407/465 and 331/406/465 claim 1 , wherein the amino acid positions of said polypeptide sequence are numbered with reference to SEQ ID NO: 2.3. The engineered galactose oxidase of claim 1 , wherein said polypeptide sequence has at least 85% claim 1 , 86% claim ...

PENICILLIN-G ACYLASES

The present invention provides engineered penicillin G acylase (PGA) enzymes, polynucleotides encoding the enzymes, compositions comprising the enzymes, and methods of using the engineered PGA enzymes. 1. An engineered penicillin G acylase capable of acylating insulin , wherein the polypeptide sequence of said penicillin G acylase is at least 85% , 90% , 91% , 92% , 93% , 94% , 95% , 96% , 97% , 98% , 99% or more identical to SEQ ID NO:2 , 4 , 12 , 24 , 40 , 56 , 70 , 82 , 100 , 108 , 110 , 116 , 136 , 142 , 154 and 160.2. The engineered penicillin G acylase of claim 1 , wherein said penicillin G acylase comprises SEQ ID NO: 2 claim 1 , 4 claim 1 , 12 claim 1 , 24 claim 1 , 40 claim 1 , 56 claim 1 , 70 claim 1 , 82 claim 1 , 108 claim 1 , 110 claim 1 , 116 claim 1 , 136 claim 1 , 142 claim 1 , 154 claim 1 , or 160.3. The engineered penicillin G acylase of claim 1 , wherein said penicillin G acylase comprises a substitution at position 436 as compared to SEQ ID NO:2 claim 1 , 4 claim 1 , 12 claim 1 , 24 claim 1 , 40 claim 1 , 56 claim 1 , 70 claim 1 , 82 claim 1 , 100 claim 1 , 108 claim 1 , 110 claim 1 , 116 claim 1 , 136 claim 1 , 142 claim 1 , 154 claim 1 , or 160.4. The engineered penicillin G acylase of claim 1 , wherein said penicillin G acylase comprises a sequence that is at least 85% claim 1 , 90% claim 1 , 91% claim 1 , 92% claim 1 , 93% claim 1 , 94% claim 1 , 95% claim 1 , 96% claim 1 , 97% claim 1 , 98% claim 1 , 99% or more identical to at least one sequence set forth in Table 5.1 claim 1 , 5.1 claim 1 , 6.1 claim 1 , 6.2 claim 1 , 6.3 claim 1 , 6.4 claim 1 , 6.5 claim 1 , 6.6 claim 1 , 6.7 claim 1 , 7.1 claim 1 , 8.1 claim 1 , 9.1 claim 1 , 11.1 claim 1 , 12.1 claim 1 , 13.1 claim 1 , 14.1 claim 1 , 15.1 claim 1 , 16.1 claim 1 , 17.1 claim 1 , 18.1 claim 1 , 19.1 claim 1 , 20.1 claim 1 , 22.1 claim 1 , 23.1 claim 1 , and/or 23.2.5. The engineered penicillin G acylase of claim 1 , wherein said penicillin G acylase comprises a sequence comprises a ...

ENGINEERED PANTOTHENATE KINASE VARIANT ENZYMES

The present invention provides engineered pantothenate kinase (PanK) enzymes, polypeptides having PanK activity, and polynucleotides encoding these enzymes, as well as vectors and host cells comprising these polynucleotides and polypeptides. Methods for producing PanK enzymes are also provided. The present invention further provides compositions comprising the PanK enzymes and methods of using the engineered PanK enzymes. The present invention finds particular use in the production of pharmaceutical compounds. 1. An engineered pantothenate kinase polypeptide comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 2 , or to a functional fragment thereof , wherein said polypeptide or fragment thereof comprises an amino acid substitution corresponding to amino acid positions 15 , 27 , and/or 283 in SEQ ID NO: 2 , wherein said polypeptide has increased ability to convert ethynyl glyceraldehyde to ethynyl glyceraldehyde phosphate when compared the wild-type polypeptide having the amino acid sequence of SEQ ID NO: 2.2. The polypeptide of claim 1 , wherein the amino acid substitution is F15L claim 1 , V27N claim 1 , or W283H.3. The polypeptide of claim 1 , wherein the amino acid substitutions are at all of the following amino acid positions: 15 claim 1 , 27 claim 1 , and 283.4. The polypeptide of claim 3 , wherein the amino acid substitutions are F15L/V27N/W283H or F15L/V27N/W283L.5. The polypeptide of claim 4 , wherein the amino acid substitutions are F15L/V27N/W283H.6. The polypeptide of claim 5 , wherein the amino acid substitutions are F15L/V27N/L277I/I281M/W283H.7. The polypeptide of claim 6 , wherein the polypeptide further comprises amino acid substitutions selected from the group consisting of amino acid positions 14/19/41/157/161/261 claim 6 , 19/22/41/44/54/119/157/261/298/308 claim 6 , 19/22/54/157/169 claim 6 , 22/106/218 claim 6 , 41 claim 6 , 41/44/54/119/120/157/169/261 claim 6 , 41/44/54/119/120/157/261/298/308 claim 6 , 41/44/ ...

PROCESSES FOR THE PREPARATION OF DEHYDROEPIANDROSTERONE AND ITS INTERMEDIATES

The present application relates to a regioselective and stereoselective processes for the preparation of dehydroepiandrosterone (DHEA) and processes for its intermediates. 2. The process of claim 1 , wherein compound of formula (I) is converted to Abiraterone acetate.3. The process of claim 1 , wherein the compound of formula (I) is converted to DHEA Enanthate.9. The process of claim 8 , wherein the ketoreductase enzyme is having Sequence ID No: 1.10. The process of claim 8 , wherein compound of formula (I) is converted to Abiraterone acetate.11. The process of claim 8 , wherein the compound of formula (I) is converted to DHEA Enanthate. The present application relates to a regioselective and stereoselective processes for the preparation of dehydroepiandrosterone (DHEA) and processes for its intermediates.Dehydroepiandrosterone (DHEA) also known as androstenolone or prasterone or 3β-hydroxyandrost-5-en-17-one or 5-androsten-3β-ol-17-one, is an important endogenous steroid hormone and has the structure of formula (I).Dehydroepiandrosterone (DHEA) is a key intermediate in the synthesis of steroidal molecules, including but not limited to abiraterone acetate, a drug used in the treatment of castration-resistant prostate cancer.An article by J. Bryan Jones et al., “Steroids and steroidases.VI. On the C-17 specificity of the Δ5-3-ketoisomerase of Psudomonas testosterone and evidence for substrate micelle formation,” Candian Journal of Chemistry, 46,1459-1465 (1968) describes a process for the preparation of androst-5-ene-3,17-dione, an intermediate used for the preparation of DHEA. The process disclosed in the said reference involves reacting androst-4-ene-3,17-dione with potassium t-butoxide in t-butyl alcohol under nitrogen atmosphere for 90 minutes at 20° C., followed by quenching the reaction mass by rapid addition of 10% aqueous acetic acid, adding excess sodium bicarbonate, extracting with ether, evaporating at room temperature and recrystallization from acetone to ...

PENICILLIN-G ACYLASES

The present invention provides engineered penicillin G acylase (PGA) enzymes, polynucleotides encoding the enzymes, compositions comprising the enzymes, and methods of using the engineered PGA enzymes. 1. An engineered penicillin G acylase variant having at least 85% sequence identity to SEQ ID NO:6 , and at least one substitution at a position selected from positions 54 , 62 , 115 , 125 , 127 , 127 , 185 , 253 , 254 , 254/255 , 254/255/370 , 255 , 256 , 257 , 257 , 260 , 268 , 322 , 325 , 348 , 369 , 370 , 372 , 373 , 377 , 378 , 384 , 384/513/536 , 388 , 389 , 391 , 435 , 461 , 517 , 530 , 554 , 556 , 557 , 559 , 560 , 600/623 , 623 , 624 , 626 , 627 , 705 , 706 , 707 , 723 , 740 , 748 , and 752 , wherein said positions are numbered with reference to SEQ ID NO:6.2. The engineered penicillin G acylase variant of claim 1 , wherein said engineered penicillin acylase variant has 85% or more sequence identity to SEQ ID NO: 6 claim 1 , and at least one substitution selected from 54C claim 1 , 62G claim 1 , 115A/P claim 1 , 125L/T claim 1 , 127S/V claim 1 , 185V claim 1 , 253K/V claim 1 , 254T claim 1 , 254W/255G claim 1 , 254W/255G/370I claim 1 , 255L claim 1 , 255M/Q/T/Y claim 1 , 256Q claim 1 , 257I claim 1 , 257V claim 1 , 260A/P claim 1 , 268S/V claim 1 , 322P claim 1 , 325G claim 1 , 348C claim 1 , 348Q claim 1 , 369L claim 1 , 369P claim 1 , 369V claim 1 , 369W claim 1 , 370F/G/S claim 1 , 372A/H/L claim 1 , 373F/M claim 1 , 377P claim 1 , 378H claim 1 , 384A claim 1 , 384F/513Q/536M claim 1 , 384G/L claim 1 , 388T claim 1 , 389L claim 1 , 391P/S claim 1 , 435R claim 1 , 461A claim 1 , 517L/P claim 1 , 530C/Y claim 1 , 554A/E/P/V claim 1 , 556G claim 1 , 557G/S claim 1 , 559P/S claim 1 , 560I claim 1 , 600T/623V claim 1 , 623A/G/R/W claim 1 , 624A claim 1 , 626G claim 1 , 627G/H claim 1 , 705G/P claim 1 , 706G claim 1 , 707S claim 1 , 723A/G claim 1 , 740L claim 1 , 748G claim 1 , and 752E.314.-. (canceled)15. The engineered penicillin G acylase variant of claim 1 ...

Penicillin-g acylases

The present invention provides engineered penicillin G acylase (PGA) enzymes, polynucleotides encoding the enzymes, compositions comprising the enzymes, and methods of using the engineered PGA enzymes.

Process for preparation of apremilast and its intermediates

Present application relates to the process for the preparation of 1-(3-Ethoxy-4-methoxy-phenyl)-2-methanesulf-onyl-ethylamine of the formula (II), its resolution and its use in preparation of Apremilast of formula (I), process for the preparation of crystalline form B of apremilast, process for preparation of amorphous form of apremilast and the crystalline form of (S)-1-(3-Eth-oxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamine of the formula (Va).

PENICILLIN-G ACYLASES

The present invention provides engineered penicillin G acylase (PGA) enzymes, polynucleotides encoding the enzymes, compositions comprising the enzymes, and methods of using the engineered PGA enzymes. 1. An engineered polynucleotide encoding an engineered penicillin G acylase capable of acylating insulin , wherein the polypeptide sequence of said penicillin G acylase is 90% or more identical to SEQ ID NO: 100 , and wherein the residue at position X67 as compared to SEQ ID NO: 100 is an alanine.2. The engineered polynucleotide encoding the engineered penicillin G acylase of claim 1 , wherein said penicillin G acylase comprises a sequence that is at least 90% or more identical to at least one sequence set forth in Table 5.1 claim 1 , 5.2 claim 1 , 6.1 claim 1 , 6.2 claim 1 , 6.3 claim 1 , 6.4 claim 1 , 6.5 claim 1 , 6.6 claim 1 , 6.7 claim 1 , 7.1 claim 1 , 8.1 claim 1 , 9.1 claim 1 , 11.1 claim 1 , 12.1 claim 1 , 13.1 claim 1 , 14.1 claim 1 , 15.1 claim 1 , 16.1 claim 1 , 17.1 claim 1 , 18.1 claim 1 , 19.1 claim 1 , 20.1 claim 1 , 22.1 claim 1 , 23.1 claim 1 , and/or 23.2.3. The engineered polynucleotide encoding the engineered penicillin G acylase of claim 1 , wherein said penicillin G acylase comprises a sequence set forth in Table 5.1 claim 1 , 5.2 claim 1 , 6.1 claim 1 , 6.2 claim 1 , 6.3 claim 1 , 6.4 claim 1 , 6.5 claim 1 , 6.6 claim 1 , 6.7 claim 1 , 7.1 claim 1 , 8.1 claim 1 , 9.1 claim 1 , 11.1 claim 1 , 12.1 claim 1 , 13.1 claim 1 , 14.1 claim 1 , 15.1 claim 1 , 16.1 claim 1 , 17.1 claim 1 , 18.1 claim 1 , 19.1 claim 1 , 22.1 claim 1 , 23.1 claim 1 , and/or Table 23.2.4. The engineered polynucleotide encoding the engineered penicillin G acylase of claim 1 , wherein said engineered penicillin G acylase comprises a polypeptide sequence selected from SEQ ID NOS:100 and 110.5. The engineered polynucleotide sequence of claim 1 , wherein said sequence comprises a polynucleotide sequence that is at least 85% claim 1 , 90% claim 1 , 91% claim 1 , 92% claim 1 , 93% ...

Penicillin-G acylases

The present invention provides engineered penicillin G acylase (PGA) enzymes, polynucleotides encoding the enzymes, compositions comprising the enzymes, and methods of using the engineered PGA enzymes.

Engineered deoxyribose-phosphate aldolases

The present invention provides engineered deoxyribose-phosphate aldolase polypeptides useful under industrial process conditions for the production of pharmaceutical and fine chemical compounds.

Engineered galactose oxidase variant enzymes

The present invention provides engineered galactose oxidase (GOase) enzymes, polypeptides having GOase activity, and polynucleotides encoding these enzymes, as well as vectors and host cells comprising these polynucleotides and polypeptides. Methods for producing GOase enzymes are also provided. The present invention further provides compositions comprising the GOase enzymes and methods of using the engineered GOase enzymes. The present invention finds particular use in the production of pharmaceutical and other compounds.

Engineered galactose oxidase variant enzymes

METHODS FOR ENZYME SYNTHESIS OF 4'-ETHYNYL 2-DEOXY NUCLEOSIDE AND COMPOUNDS

SÍNTESE ENZIMÁTICA DE ANÁLOGOS DE NUCLEOSÍDEO 4'-ETINILA. A presente invenção se refere a uma síntese enzimática de nucleosídeos de 4'-etinil-2'-desóxi e análogos dos mesmos, por exemplo EFdA, que elimina o uso de grupos de proteção nos intermediários, aprimora a estereosseletividade de glicosilação e reduz o número de etapas de processo necessárias para fazer os referidos compostos. Também se refere aos novos intermediários empregados no processo. ENZYME SYNTHESIS OF 4'-ETYNYL NUCLEOSIDE ANALOGS. The present invention relates to an enzymatic synthesis of 4'-ethynyl-2'-deoxy nucleosides and analogues thereof, for example EFdA, which eliminates the use of protecting groups in the intermediates, improves the glycosylation stereoselectivity and reduces the number of process steps necessary to make said compounds. It also refers to the new intermediaries employed in the process.

Processes for the preparation of dehydroepiandrosterone and its intermediates

The present application relates to a regioselective and stereoselective processes for the preparation of dehydroepiandrosterone (DHEA) and processes for its intermediates.

Engineered pantothenate kinase variant enzymes

The present invention provides engineered pantothenate kinase (PanK) enzymes, polypeptides having PanK activity, and polynucleotides encoding these enzymes, as well as vectors and host cells comprising these polynucleotides and polypeptides. Methods for producing PanK enzymes are also provided. The present invention further provides compositions comprising the PanK enzymes and methods of using the engineered PanK enzymes. The present invention finds particular use in the production of pharmaceutical compounds.

Enzymatic synthesis of 4'-ethynyl nucleoside analogs

The present invention relates to an enzymatic synthesis of 4'-ethynyl-2'-deoxy nucleosides and analogs thereof, for example EFdA, that eliminates the use of protecting groups on the intermediates, improves the stereoselectivity of glycosylation and reduces the number of process steps needed to make said compounds. It also relates to the novel intermediates employed in the process.

Penicillin-g acylases.

La presente invencion proporciona enzimas disenadas de penicilina G acilasa (PGA), polinucleotidos que codifican dichas enzimas, composiciones que incluyen las enzimas y métodos para usar las enzimas de PGA disenadas.

Engineered galactose oxidase variant enzymes

The present invention provides engineered galactose oxidase (GOase) enzymes, polypeptides having GOase activity, and polynucleotides encoding these enzymes, as well as vectors and host cells comprising these polynucleotides and polypeptides. Methods for producing GOase enzymes are also provided. The present invention further provides compositions comprising the GOase enzymes and methods of using the engineered GOase enzymes. The present invention finds particular use in the production of pharmaceutical and other compounds.

Engineered deoxyribose-phosphate aldolases

The present invention provides engineered deoxyribose-phosphate aldolase polypeptides useful under industrial process conditions for the production of pharmaceutical and fine chemical compounds.

Engineered galactose oxidase variant enzymes

The present invention provides engineered galactose oxidase (GOase) enzymes, polypeptides having GOase activity, and polynucleotides encoding these enzymes, as well as vectors and host cells comprising these polynucleotides and polypeptides. Methods for producing GOase enzymes are also provided. The present invention further provides compositions comprising the GOase enzymes and methods of using the engineered GOase enzymes. The present invention finds particular use in the production of pharmaceutical and other compounds.

Penicillin-g acylases

The present invention provides engineered penicillin G acylase (PGA) enzymes, polynucleotides encoding the enzymes, compositions comprising the enzymes, and methods of using the engineered PGA enzymes.

Engineered deoxyribose-phosphate aldolases

The present invention provides engineered deoxyribose-phosphate aldolase polypeptides useful under industrial process conditions for the production of pharmaceutical and fine chemical compounds.

Engineered galactose oxidase variant enzymes

Synthesis of uridine

The present invention relates to efficient synthetic processes useful in the preparation of uridine, which is useful in the production of nucleosides and nucleotides that may be active as antiviral agents, as well as compositions and methods thereof.

Penicillin-G acylases

The present invention provides engineered penicillin G acylase (PGA) enzymes, polynucleotides encoding the enzymes, compositions comprising the enzymes, and methods of using the engineered PGA enzymes.

Synthesis of antiviral nucleosides

The present invention relates to efficient synthetic processes useful in the preparation of antiviral nucleosides, particularly uridine 4-oxime 5'-(2-methylpropanoate) {(2R,3S,4R,5R)-3,4-dihydroxy-5-[4-(hydroxyimino)-2-oxo-3,4-dihydropyrimidin-1(2H)-yl]oxolan-2-yl}methyl 2-methylpropanoate and pharmaceutically acceptable salts, derivatives, tautomers, isomers, and prodrugs of, which may be active as antiviral agents, as well as compositions and methods thereof. The present invention also encompasses intermediates useful in the disclosed synthetic processes and the methods of their preparation.

４’－エチルヌクレオシド類似体の酵素的合成

【課題】中間体上の保護基の使用を排除し、グリコシル化の立体選択性を改善し、化合物を製造するのに必要なプロセス段階の数を減少させる、４’－エチニル２’－デオキシヌクレオシドおよびその類似体の合成法を提供する。【解決手段】４’－エチニル２’－デオキシヌクレオシドまたはその類似体の合成方法であって、マンガン（ＩＩ）塩を含む緩衝液中で化合物６．５TIFF2023123750000080.tif24145［式中、２Ｘ＋は（ａ）２つのプロトン、（ｂ）１つのプロトンと１つの１価カチオン、（ｃ）同一または異なる２つの１価カチオン、または（ｄ）１つの２価カチオンである。］をプリンヌクレオシドホスホリラ－ゼおよびヌクレオ塩基もしくはその類似体と組合せることを含む、合成方法とする。【選択図】なし

Penicillin-g acylases

The present invention provides engineered penicillin G acylase (PGA) enzymes, polynucleotides encoding the enzymes, compositions comprising the enzymes, and methods of using the engineered PGA enzymes.

Synthesis of antiviral nucleosides

The present invention relates to efficient synthetic processes useful in the preparation of antiviral nucleosides, particularly uridine 4-oxime 5′-(2-methylpropanoate) {(2R,3S,4R,5R)-3,4-dihydroxy-5-[4-(hydroxyimino)-2-oxo-3,4-dihydropyrimidin-1(2H)-yl]oxolan-2-yl}methyl 2-methylpropanoate and pharmaceutically acceptable salts, derivatives, tautomers, isomers, and prodrugs of, which may be active as antiviral agents, as well as compositions and methods thereof. The present invention also encompasses intermediates useful in the disclosed synthetic processes and the methods of their preparation.

Synthesis of uridine

The present invention relates to efficient synthetic processes useful in the preparation of uridine, which is useful in the production of nucleosides and nucleotides that may be active as antiviral agents, as well as compositions and methods thereof.

Synthesis of antiviral nucleosides

Sintesis de nucleosidos antivirales.

La presente invención se relaciona con procesos sintéticos eficientes útiles en la preparación de nucleósidos antivirales, particularmente uridina 4-oxima 5'-(2-metilpropanoato) {(2R,3S,4R,5R)-3,4-dihidroxi-5-[4-(hidroxiimino)-2-oxo-3,4-dihidr opirimidin-1(2H)-il]oxolan-2-il}metil 2-metilpropanoato y sales, derivados, tautómeros, isómeros y profármacos farmacéuticamente aceptables, que pueden ser activos como agentes antivirales, así como sus composiciones y métodos. La presente invención también abarca intermediarios útiles en los procesos sintéticos divulgados y los métodos para su preparación.

Engineered galactose oxidase variant enzymes

The present invention provides engineered galactose oxidase (GOase) enzymes, polypeptides having GOase activity, and polynucleotides encoding these enzymes, as well as vectors and host cells comprising these polynucleotides and polypeptides. Methods for producing GOase enzymes are also provided. The present invention further provides compositions comprising the GOase enzymes and methods of using the engineered GOase enzymes. The present invention finds particular use in the production of pharmaceutical and other compounds.

Enzymatic synthesis of 4′-ethynyl nucleoside analogs

The present invention relates to an enzymatic synthesis of 4′-ethynyl-2′-deoxy nucleosides and analogs thereof, for example EFdA, that eliminates the use of protecting groups on the intermediates, improves the stereoselectivity of glycosylation and reduces the number of process steps needed to make said compounds. It also relates to the novel intermediates employed in the process.

Engineered galactose oxidase variant enzymes

The present invention provides engineered galactose oxidase (GOase) enzymes, polypeptides having GOase activity, and polynucleotides encoding these enzymes, as well as vectors and host cells comprising these polynucleotides and polypeptides. Methods for producing GOase enzymes are also provided. The present invention further provides compositions comprising the GOase enzymes and methods of using the engineered GOase enzymes. The present invention finds particular use in the production of pharmaceutical and other compounds.

Enzymatic synthesis of 4'-ethynyl nucleoside analogs

The present invention relates to an enzymatic synthesis of 4′-ethynyl-2′-deoxy nucleosides and analogs thereof, for example EFdA, that eliminates the use of protecting groups on the intermediates, improves the stereoselectivity of glycosylation and reduces the number of process steps needed to make said compounds. It also relates to the novel intermediates employed in the process.

Penicillin-G acylases

The present invention provides engineered penicillin G acylase (PGA) enzymes, polynucleotides encoding the enzymes, compositions comprising the enzymes, and methods of using the engineered PGA enzymes.

Engineered pantothenate kinase variant enzymes

The present invention provides engineered pantothenate kinase (PanK) enzymes, polypeptides having PanK activity, and polynucleotides encoding these enzymes, as well as vectors and host cells comprising these polynucleotides and polypeptides. Methods for producing PanK enzymes are also provided. The present invention further provides compositions comprising the PanK enzymes and methods of using the engineered PanK enzymes. The present invention finds particular use in the production of pharmaceutical compounds.