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    Enzymatic resolution of aryl and thio-substituted acids
    1.
    发明授权
    Enzymatic resolution of aryl and thio-substituted acids 失效
    芳基和硫取代的酸的酶解

    公开(公告)号：US06620600B2

    公开(公告)日：2003-09-16

    申请号：US09946722

    申请日：2001-09-05

    申请人： Jingyang Zhu ,  Li You ,  Brenda J. White ,  Shannon X. Zhao ,  Paul M. Skonezny

    发明人： Jingyang Zhu ,  Li You ,  Brenda J. White ,  Shannon X. Zhao ,  Paul M. Skonezny

    IPC分类号： C12P1100

    CPC分类号： H01M4/136 ,  C07C67/343 ,  C12P7/40 ,  C12P7/62 ,  C12P11/00 ,  C12P41/005 ,  H01M4/366 ,  H01M4/485 ,  H01M4/525 ,  H01M4/5825 ,  H01M4/625 ,  H01M10/052 ,  H01M10/0525 ,  H01M2004/027 ,  C07C69/738

    摘要： Provided is a method of resolving a racemic mixture of a compound of formula I to obtain a desired enantiomer: wherein Ar is C6 or C10 aromatic group that can be substituted with H, C1 to C6 alkyl, trifluoromethyl or halo, R5 is halo or —S—R1, wherein R1 is H or acetyl, and R2 is H or C1 to C6 alkyl, the method comprising: reacting a compound of formula I wherein the compound is an ester whereby R2 is C1 to C6 alkyl with a lipase derived from Mucor meihei to stereoselectively hydrolyze the ester bond to produce an acid; and isolating the acid, wherein the reaction is conducted in a solvent comprising 80% to 98% v/v % organic phase and a residue of water phase (which can be buffered).

    摘要翻译： 提供一种拆分式I化合物的外消旋混合物以获得所需对映体的方法：其中Ar为可被H，C 1至C 6烷基，三氟甲基或卤素取代的C 6或C 10芳族基团，R 5为卤素或 - S-R1，其中R1是H或乙酰基，R2是H或C1-C6烷基，所述方法包括：使式I化合物，其中化合物是酯，其中R2是C1-C6烷基和衍生自毛霉素的脂肪酶 咪唑立体选择性地水解酯键以产生酸; 并分离酸，其中反应在包含80％至98％v / v％有机相和水相残余物（可缓冲）的溶剂中进行。

    Enzymatic resolution of aryl and thio-substituted acids
    2.
    发明授权
    Enzymatic resolution of aryl and thio-substituted acids 失效
    芳基和硫取代的酸的酶解

    公开(公告)号：US07026143B2

    公开(公告)日：2006-04-11

    申请号：US10625404

    申请日：2003-07-23

    申请人： Jingyang Zhu ,  Li You ,  Brenda J. White ,  Shannon X. Zha ,  Paul M. Skonezny

    发明人： Jingyang Zhu ,  Li You ,  Brenda J. White ,  Shannon X. Zha ,  Paul M. Skonezny

    IPC分类号： C12P11/00

    CPC分类号： H01M4/136 ,  C07C67/343 ,  C12P7/40 ,  C12P7/62 ,  C12P11/00 ,  C12P41/005 ,  H01M4/366 ,  H01M4/485 ,  H01M4/525 ,  H01M4/5825 ,  H01M4/625 ,  H01M10/052 ,  H01M10/0525 ,  H01M2004/027 ,  C07C69/738

    摘要： Provided is a method of resolving a racemic mixture of a compound of formula I to obtain a desired enantiomer: wherein Ar is C6 or C10 aromatic group that can be substituted with H, C1 to C6 alkyl, trifluoromethyl or halo, R5 is halo or —S—R1, wherein R1 is H or acetyl, and R2 is H or C1 to C6 alkyl, the method comprising: reacting a compound of formula I wherein the compound is an ester whereby R2 is C1 to C6 alkyl with a lipase derived from Mucor meihei to stereoselectively hydrolyze the ester bond to produce an acid; and isolating the acid, wherein the reaction is conducted in a solvent comprising 80% to 98% v/v % organic phase and a residue of water phase (which can be buffered).

    摘要翻译： 提供了一种拆分式I化合物的外消旋混合物以获得所需对映异构体的方法：其中Ar是可以被取代的C 6或C 10芳族基团 H，C 1至C 6烷基，三氟甲基或卤素，R 5是卤素或-SR 1， 其中R 1是H或乙酰基，R 2是H或C 1 -C 6烷基，其中R 1是H或乙酰基，R 2是H或C 1 -C 6烷基， 方法包括：使式I化合物，其中所述化合物是酯，其中R 2是C 1 -C 6烷基与脂肪酶衍生的 从Mucor meihei到立体选择性地水解酯键以产生酸; 并分离酸，其中反应在包含80％至98％v / v％有机相和水相残余物（可缓冲）的溶剂中进行。

    Rhodococcus erythropolis strain
    3.
    发明授权
    Rhodococcus erythropolis strain 有权
    红球菌红细菌菌株

    公开(公告)号：US08119389B2

    公开(公告)日：2012-02-21

    申请号：US12506596

    申请日：2009-07-21

    申请人： Nigel Ian Bowers ,  Paul M. Skonezny ,  Gregory L. Stein ,  Thomas Franceschini ,  Shu-Jen Chiang ,  Wendy L. Anderson ,  Li You ,  Zizhuo Xing

    发明人： Nigel Ian Bowers ,  Paul M. Skonezny ,  Gregory L. Stein ,  Thomas Franceschini ,  Shu-Jen Chiang ,  Wendy L. Anderson ,  Li You ,  Zizhuo Xing

    IPC分类号： C12N1/20

    CPC分类号： C12R1/01 ,  C12P13/001

    摘要： The present invention relates to a process for preparing (2R,3S)-1-halo-2-hydroxy-3-(protected)amino-4-substituted butane comprising contacting a mutagenized Rhodococcus erythropolis having ATCC deposit no. PTA-6648 with (3S)-1-halo-2-oxo-3-(protected)amino-4-substituted butane substrate. The present invention also relates to a process comprising mixing (2R,3S)-1-halo-2-hydroxy-3-(protected)amino-4-substituted butane with at least one base in the presence of at least one solvent to produce a reaction mixture containing (2R,3S)-1,2-epoxy-3-(protected)amino-4-substituted butane. The present invention further relates to a process comprising crystallizing the (2R,3S)-1,2-epoxy-3-(protected)amino-4-substituted butane out of the reaction mixture by concurrently adding water and the reaction mixture together. The present invention is also directed to a mutagenized Rhodococcus erythropolis having ATCC deposit no. PTA-6648.

    摘要翻译： 本发明涉及制备（2R，3S）-1-卤代-2-羟基-3-（被保护的）氨基-4-取代的丁烷的方法，包括将具有ATCC保藏号的诱变的红球菌红景天 （3S）-1-卤代-2-氧代-3-（保护的）氨基-4-取代的丁烷底物的PTA-6648。 本发明还涉及一种方法，其包括在至少一种溶剂的存在下将（2R，3S）-1-卤代-2-羟基-3-（保护的）氨基-4-取代的丁烷与至少一个碱混合以产生 含有（2R，3S）-1,2-环氧-3-（保护）氨基-4-取代丁烷的反应混合物。 本发明还涉及通过将水和反应混合物同时加入，使（2R，3S）-1,2-环氧-3-（被保护的）氨基-4-取代丁烷从反应混合物中结晶出来的方法。 本发明还涉及具有ATCC保藏号的诱变的红球菌红球菌。 PTA-6648。

    Process for preparing (2R,3S)-1,2-epoxy-3-(protected)amino-4-substituted butane and intermediates thereof
    4.
    发明授权
    Process for preparing (2R,3S)-1,2-epoxy-3-(protected)amino-4-substituted butane and intermediates thereof 有权
    制备（2R，3S）-1,2-环氧-3-（保护）氨基-4-取代丁烷的方法及其中间体

    公开(公告)号：US07582468B2

    公开(公告)日：2009-09-01

    申请号：US11365275

    申请日：2006-03-01

    申请人： Nigel Ian Bowers ,  Paul M. Skonezny ,  Gregory L. Stein ,  Thomas Franceschini ,  Shu-Jen Chiang ,  Wendy L. Anderson ,  Li You ,  Zizhuo Xing

    发明人： Nigel Ian Bowers ,  Paul M. Skonezny ,  Gregory L. Stein ,  Thomas Franceschini ,  Shu-Jen Chiang ,  Wendy L. Anderson ,  Li You ,  Zizhuo Xing

    IPC分类号： C12P41/00

    CPC分类号： C12R1/01 ,  C12P13/001

    摘要： The present invention relates to a process for preparing (2R,3S)-1-halo-2-hydroxy-3-(protected)amino-4-substituted butane comprising contacting a mutagenized Rhodococcus erythropolis having ATCC deposit no. PTA-6648 with (3S)-1-halo-2-oxo-3-(protected)amino-4-substituted butane substrate. The present invention also relates to a process comprising mixing (2R,3S)-1-halo-2-hydroxy-3-(protected)amino-4-substituted butane with at least one base in the presence of at least one solvent to produce a reaction mixture containing (2R,3S)-1,2-epoxy-3-(protected)amino-4-substituted butane. The present invention further relates to a process comprising crystallizing the (2R,3S)-1,2-epoxy-3-(protected)amino-4-substituted butane out of the reaction mixture by concurrently adding water and the reaction mixture together. The present invention is also directed to a mutagenized Rhodococcus erythropolis having ATCC deposit no. PTA-6648.

    摘要翻译： 本发明涉及制备（2R，3S）-1-卤代-2-羟基-3-（被保护的）氨基-4-取代的丁烷的方法，包括将具有ATCC保藏号的诱变的红球菌红景天 （3S）-1-卤代-2-氧代-3-（保护的）氨基-4-取代的丁烷底物的PTA-6648。 本发明还涉及一种方法，其包括在至少一种溶剂的存在下将（2R，3S）-1-卤代-2-羟基-3-（保护的）氨基-4-取代的丁烷与至少一个碱混合以产生 含有（2R，3S）-1,2-环氧-3-（保护）氨基-4-取代丁烷的反应混合物。 本发明还涉及通过将水和反应混合物同时加入，使（2R，3S）-1,2-环氧-3-（被保护的）氨基-4-取代丁烷从反应混合物中结晶出来的方法。 本发明还涉及具有ATCC保藏号的诱变的红球菌红球菌。 PTA-6648。

    PROCESS FOR PREPARING (2R,3S)-1,2-EPOXY-3-(PROTECTED) AMINO-4-SUBSTITUTED BUTANE AND INTERMEDIATES THEREOF
    5.
    发明申请
    PROCESS FOR PREPARING (2R,3S)-1,2-EPOXY-3-(PROTECTED) AMINO-4-SUBSTITUTED BUTANE AND INTERMEDIATES THEREOF 有权
    制备（2R，3S）-1,2-环氧-3-（保护的）氨基-4-取代的丁烷的方法及其中间体

    公开(公告)号：US20090286303A1

    公开(公告)日：2009-11-19

    申请号：US12506596

    申请日：2009-07-21

    申请人： Nigel Ian Bowers ,  Paul M. Skonezny ,  Gregory L. Stein ,  Thomas Franceschini ,  Shu-Jen Chiang ,  Wendy L. Anderson ,  Li You ,  Zizhuo Xing

    发明人： Nigel Ian Bowers ,  Paul M. Skonezny ,  Gregory L. Stein ,  Thomas Franceschini ,  Shu-Jen Chiang ,  Wendy L. Anderson ,  Li You ,  Zizhuo Xing

    IPC分类号： C12N1/21

    CPC分类号： C12R1/01 ,  C12P13/001

    摘要： The present invention relates to a process for preparing (2R,3S)-1-halo-2-hydroxy-3-(protected)amino-4-substituted butane comprising contacting a mutagenized Rhodococcus erythropolis having ATCC deposit no. PTA-6648 with (3S)-1-halo-2-oxo-3-(protected)amino-4-substituted butane substrate. The present invention also relates to a process comprising mixing (2R,3S)-1-halo-2-hydroxy-3-(protected)amino-4-substituted butane with at least one base in the presence of at least one solvent to produce a reaction mixture containing (2R,3S)-1,2-epoxy-3-(protected)amino-4-substituted butane. The present invention further relates to a process comprising crystallizing the (2R,3S)-1,2-epoxy-3-(protected)amino-4-substituted butane out of the reaction mixture by concurrently adding water and the reaction mixture together. The present invention is also directed to a mutagenized Rhodococcus erythropolis having ATCC deposit no. PTA-6648.

    摘要翻译： 本发明涉及制备（2R，3S）-1-卤代-2-羟基-3-（被保护的）氨基-4-取代的丁烷的方法，其包括将具有ATCC保藏号的诱变的红球菌红景天 （3S）-1-卤代-2-氧代-3-（保护的）氨基-4-取代的丁烷底物的PTA-6648。 本发明还涉及一种方法，其包括在至少一种溶剂的存在下将（2R，3S）-1-卤代-2-羟基-3-（保护的）氨基-4-取代的丁烷与至少一个碱混合以产生 含有（2R，3S）-1,2-环氧-3-（保护）氨基-4-取代丁烷的反应混合物。 本发明还涉及通过将水和反应混合物同时加入，使（2R，3S）-1,2-环氧-3-（被保护的）氨基-4-取代丁烷从反应混合物中结晶出来的方法。 本发明还涉及具有ATCC保藏号的诱变的红球菌红球菌。 PTA-6648。

    Compositions and methods for hydroxylating epothilones
    7.
    发明授权
    Compositions and methods for hydroxylating epothilones 有权
    用于羟化埃坡霉素的组合物和方法

    公开(公告)号：US07214527B2

    公开(公告)日：2007-05-08

    申请号：US10915172

    申请日：2004-08-09

    申请人： Jonathan David Basch ,  Shu-Jen David Chiang ,  Suo-Win Liu ,  Akbar Nayeem ,  Yuhua Sun ,  Li You

    发明人： Jonathan David Basch ,  Shu-Jen David Chiang ,  Suo-Win Liu ,  Akbar Nayeem ,  Yuhua Sun ,  Li You

    IPC分类号： C12N1/20 ,  C12N15/74 ,  C07H21/04

    CPC分类号： C12N9/0077 ,  C07K14/79 ,  C07K2299/00 ,  C12P17/181

    摘要： Isolated nucleic acid sequences and polypeptides encoded thereby for epothilone B hydroxylase and mutants and variants thereof and a ferredoxin located downstream from the epothilone B hydroxylase gene are provided. Also provided are vectors and cells containing these vectors. In addition, methods for producing recombinant microorganisms, methods for using these recombinant microorganism to produce hydroxyalkyl-bearing epothilones and an epothilone analog produced by a mutant of epothilone B hydroxylase are provided.

    摘要翻译： 提供了分离的核酸序列和由此编码的用于埃坡霉素B羟化酶及其突变体和变体以及位于埃坡霉素B羟化酶基因下游的铁氧还蛋白的多肽。 还提供了含有这些载体的载体和细胞。 此外，提供了用于制备重组微生物的方法，使用这些重组微生物制备含有羟烷基的埃坡霉素的方法和由埃坡霉素B羟化酶的突变体产生的埃坡霉素类似物。

    Compositions and methods for hydroxylating epothilones
    9.
    发明授权
    Compositions and methods for hydroxylating epothilones 失效
    用于羟化埃坡霉素的组合物和方法

    公开(公告)号：US06884608B2

    公开(公告)日：2005-04-26

    申请号：US10321188

    申请日：2002-12-17

    申请人： Jonathan David Basch ,  Shu-Jen David Chiang ,  Suo-Win Liu ,  Akbar Nayeem ,  Yuhua Sun ,  Li You

    发明人： Jonathan David Basch ,  Shu-Jen David Chiang ,  Suo-Win Liu ,  Akbar Nayeem ,  Yuhua Sun ,  Li You

    IPC分类号： C07K14/79 ,  C12N9/02 ,  C12P17/18

    CPC分类号： C12N9/0077 ,  C07K14/79 ,  C07K2299/00 ,  C12P17/181

    摘要： Isolated nucleic acid sequences and polypeptides encoded thereby for epothilone B hydroxylase and mutants and variants thereof and a ferredoxin located downstream from the epothilone B hydroxylase gene are provided. Also provided are vectors and cells containing these vectors. In addition, methods for producing recombinant microorganisms, methods for using these recombinant microorganism to produce hydroxyalkyl-bearing epothilones and an epothilone analog produced by a mutant of epothilone B hydroxylase are provided.

    摘要翻译： 提供了分离的核酸序列和由此编码的用于埃坡霉素B羟化酶及其突变体和变体以及位于埃坡霉素B羟化酶基因下游的铁氧还蛋白的多肽。 还提供了含有这些载体的载体和细胞。 此外，提供了用于制备重组微生物的方法，使用这些重组微生物制备含有羟烷基的埃坡霉素的方法和由埃坡霉素B羟化酶的突变体产生的埃坡霉素类似物。