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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：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。

    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：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。

    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。

    Rhodococcus erythropolis strain
    6.
    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
    7.
    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。