公开(公告)号：US4886750A

公开(公告)日：1989-12-12

申请号：US674

申请日：1987-01-06

申请人： Mauro A. Bertola ,  Arthur F. Marx ,  Hein S. Koger ,  Wilhelmus J. Quax ,  Cornelis J. Van der Laken ,  Gareth T. Phillips ,  Brian W. Robertson ,  Peter D. Watts

发明人： Mauro A. Bertola ,  Arthur F. Marx ,  Hein S. Koger ,  Wilhelmus J. Quax ,  Cornelis J. Van der Laken ,  Gareth T. Phillips ,  Brian W. Robertson ,  Peter D. Watts

IPC分类号： C12N15/09 ,  A61K31/19 ,  A61K31/33 ,  A61P25/04 ,  A61P29/00 ,  C07C57/30 ,  C07D209/46 ,  C07H21/04 ,  C12N1/20 ,  C12N1/21 ,  C12N9/18 ,  C12N15/00 ,  C12P7/40 ,  C12P17/00 ,  C12P41/00 ,  C12R1/06 ,  C12R1/10 ,  C12R1/125 ,  C12R1/19 ,  C12R1/38 ,  C12R1/385 ,  C12R1/39 ,  C12R1/40 ,  C12R1/465 ,  C12R1/785

CPC分类号： C12P41/005 ,  C12N9/18 ,  C12P17/00 ,  C12P7/40 ,  Y10S435/822 ,  Y10S435/83 ,  Y10S435/836 ,  Y10S435/839 ,  Y10S435/849 ,  Y10S435/874 ,  Y10S435/886

摘要： A process for the preparation of a pharmaceutically active compound in a stereospecific form of the formula ##STR1## or a pharmaceutically acceptable salt or ester thereof, like an alkali metal salt or an alkaline earth metal salt or a pivaloyl ester, wherein R.sub.1 represents an optionally substituted aryl group such as a phenyl or naphthyl group optionally included in a heterocyclic ring system, which is optionally substituted, or represents a heteroaromatic ring system containing in addition to carbon atoms one or more atoms selected from nitrogen, sulphur and oxygen, this ring system being optionally substituted, which comprises subjecting a compound of the formula ##STR2## wherein R.sub.1 is an ester residue and preferably an alkyl group optionally substituted, to the action of a micro-organism having the ability for stereoselective hydrolysis of compound (II) into compound (I), having at least 80% by weight the S-configuration, and if desired converting compound (I) into the pharmaceutically acceptable salt or ester thereof.

公开(公告)号：US5037751A

公开(公告)日：1991-08-06

申请号：US405553

申请日：1989-09-11

申请人： Mauro A. Bertola ,  Arthur F. Marx ,  Hein S. Koger ,  Wilhelmus J. Quax ,  Cornelis J. van der Laken ,  Gareth T. Phillips ,  Brian W. Robertson ,  Peter D. Watts

发明人： Mauro A. Bertola ,  Arthur F. Marx ,  Hein S. Koger ,  Wilhelmus J. Quax ,  Cornelis J. van der Laken ,  Gareth T. Phillips ,  Brian W. Robertson ,  Peter D. Watts

IPC分类号： C12N15/09 ,  A61K31/19 ,  A61K31/33 ,  A61P25/04 ,  A61P29/00 ,  C07C57/30 ,  C07D209/46 ,  C07H21/04 ,  C12N1/20 ,  C12N1/21 ,  C12N9/18 ,  C12N15/00 ,  C12P7/40 ,  C12P17/00 ,  C12P41/00 ,  C12R1/06 ,  C12R1/10 ,  C12R1/125 ,  C12R1/19 ,  C12R1/38 ,  C12R1/385 ,  C12R1/39 ,  C12R1/40 ,  C12R1/465 ,  C12R1/785

CPC分类号： C12P41/005 ,  C12N9/18 ,  C12P17/00 ,  C12P7/40 ,  Y10S435/822 ,  Y10S435/83 ,  Y10S435/836 ,  Y10S435/839 ,  Y10S435/849 ,  Y10S435/874 ,  Y10S435/886

摘要： A process for the preparation of a pharmaceutically active compound in a stereospecific form of the formula ##STR1## or a pharmaceutically acceptable salt or ester thereof, like an alkali metal salt or an alkaline earth metal salt or a pivaloyl ester, wherein R.sub.1 represents an optionally substituted aryl group such as a phenyl or naphthyl group optionally included in a heterocyclic ring system, which is optionally substituted, or represents a heteroaromatic ring system containing in addition to carbon atoms one or more atoms selected from nitrogen, sulphur and oxygen, this ring system being optionally substituted, which comprises subjecting a compound of the formula ##STR2## wherein R.sub.2 is an ester residue and preferably an alkyl group optionally substituted, to the action of a micro-organism having the ability for stereoselective hydrolysis of compound (II) into compound (I), having at least 80% by weight the S-configuration, and if desired converting compound (I) into the pharmaceutically acceptable salt or ester thereof.

公开(公告)号：US4956284A

公开(公告)日：1990-09-11

申请号：US826791

申请日：1986-02-06

申请人： Gareth T. Phillips ,  Brian W. Robertson ,  Mauro A. Bertola ,  Hein S. Koger ,  Arthur F. Marx ,  Peter D. Watts

发明人： Gareth T. Phillips ,  Brian W. Robertson ,  Mauro A. Bertola ,  Hein S. Koger ,  Arthur F. Marx ,  Peter D. Watts

IPC分类号： C07C213/04 ,  C07D303/24 ,  C12P17/02

CPC分类号： C07C213/04 ,  C07D303/24 ,  C12P17/02 ,  Y10S435/863 ,  Y10S435/872 ,  Y10S435/874

摘要： A process for the preparation of metoprolol in a stereospecific form or a non-toxic, pharmaceutically acceptable acid addition salt thereof and/or a stereospecific form of 4-(2-methoxyethyl)-phenyl glycidyl ether which comprises subjecting 4-(2-methoxyethyl)-phenyl allyl ether to the action of a microorganism having the ability for stereoselective epoxidation of 4-(2-methoxyethyl)-phenyl allyl ether into 4-(2-methoxyethyl)-phenyl glycidyl ether having at least 80% by weight the S configuration, at least partly separating 4-(2-methoxyethyl)-phenyl glycidyl ether and/or reacting 4-(2-methoxyethyl)-phenyl glycidyl ether with isopropylamine and at least partly separating metoprolol and/or converting metoprolol into its non-toxic, pharmaceutically acceptable acid addition salt.

摘要翻译： 以立体特异性形式或无毒的药学上可接受的酸加成盐和/或立体特异性形式的4-（2-甲氧基乙基） - 苯基缩水甘油醚制备美托洛尔的方法，其包括使4-（2-甲氧基乙基） （4-甲氧基乙基） - 苯基烯丙基醚的4-（2-甲氧基乙基） - 苯基缩水甘油醚的立体选择性环氧化反应能力的微生物的作用，其具有至少80重量％的S 至少部分分离4-（2-甲氧基乙基） - 苯基缩水甘油醚和/或使4-（2-甲氧基乙基） - 苯基缩水甘油醚与异丙胺反应，并至少部分分离美托洛尔和/或将美托洛尔转化为无毒的 ，药学上可接受的酸加成盐。

公开(公告)号：US5190867A

公开(公告)日：1993-03-02

申请号：US822653

申请日：1992-01-21

申请人： Mauro A. Bertola ,  Arthur F. Marx ,  Hein S. Koger ,  Volkert P. Claassen ,  Gareth T. Phillips

发明人： Mauro A. Bertola ,  Arthur F. Marx ,  Hein S. Koger ,  Volkert P. Claassen ,  Gareth T. Phillips

IPC分类号： C07D317/20 ,  C07D317/32 ,  C07D317/72 ,  C12P41/00

CPC分类号： C07D317/72 ,  C07D317/20 ,  C07D317/32 ,  C12P41/001 ,  C12R1/15 ,  C12R1/32 ,  C12R1/365

摘要： Process for the preparation of R-2,2-R.sub.1,R.sub.2 -1,3-dioxolane-4-methanol wherein R.sub.1 and R.sub.2 are H or alkyl groups or wherein R.sub.1 and R.sub.2 together with the carbon atom to which they are attached form a carbocyclic ring by subjecting a mixture of R- and S-2,2-R.sub.1,R.sub.2 -1,3-dioxolane-4-methanol to the action of a micro-organism or substances derived therefrom having the ability for stereoselective consumption of S-2,2-R.sub.1,R.sub.2 -1,3-dioxolane-4-methanol preferably until at least 80 wt % and more preferably all the S-2,2-R.sub.1,R.sub.2 -1,3-dioxolane-4-methanol is consumed. Various micro-organisms of the genus Rhodococcus, Nocardia and Corynebacterium are disclosed as suitable for the purpose. The R-isomer is a valuable intermediate for stereospecific synthesis of various biologically active compounds including S-metoprolol.

摘要翻译： 制备R-2,2-R1，R2-1,3-二氧戊环-4-甲醇的方法，其中R 1和R 2为H或烷基或其中R 1和R 2与它们所连接的碳原子一起形成 通过使R-和S-2,2-R1，R2-1,3-二氧戊环-4-甲醇的混合物经受微生物或其衍生物质的作用，具有立体选择性消耗S- 优选直到至少80重量％，更优选全部S-2,2-R 1，R 2，1,3-二氧戊环-4-甲醇被消耗 。 公开了红球菌属，诺卡氏菌属和棒状杆菌属的各种微生物，以适合此目的。 R-异构体是用于立体特异性合成各种生物活性化合物（包括S-美托洛尔）的有价值的中间体。