公开(公告)号：US5098841A

公开(公告)日：1992-03-24

申请号：US360802

申请日：1989-06-02

Applicant: Oreste Ghisalba ,  Daniel Gygax ,  Rente Lattmann ,  Hans-Peter Schar ,  Elke Schmidt ,  Gottfried Sedelmeier

Inventor： Oreste Ghisalba ,  Daniel Gygax ,  Rente Lattmann ,  Hans-Peter Schar ,  Elke Schmidt ,  Gottfried Sedelmeier

IPC: C12P7/52 ,  C07C51/367 ,  C07K5/078 ,  C12P7/42 ,  C12R1/45

CPC classification number: C12P7/42 ,  C07C51/367 ,  C07K5/06139

Abstract: The invention relates to a preferably continuous process for the preparation of R- or S-2-hydroxy-4-phenylbutyric acid in very high enantiomeric purity, which comprises reducing 2-oxo-4-phenylbutyric acid with the enzyme D-lactate dehydrogenase from Staphylococcus epidermidis or with the enzyme L-lactate dehydrogenase from bovine heart, respectively, in the presence of NAD(H) and formate or ethanol and formate dehydrogenase or alcohol dehydrogenase, respectively. R-2-hydroxy-4-phenylbutyric acid is a valuable intermediate in the preparation of ACE inhibitors or their precursors.

Abstract translation: 本发明涉及用于制备非常高对映体纯度的R-或S-2-羟基-4-苯基丁酸的优选连续方法，其包括用D-乳酸脱氢酶酶将2-氧代-4-苯基丁酸与 分别在NAD（H）和甲酸盐或乙醇和甲酸脱氢酶或醇脱氢酶存在下分别从牛心脏分泌表皮葡萄球菌或L-乳酸脱氢酶酶。 R-2-羟基-4-苯基丁酸是制备ACE抑制剂或其前体的有价值的中间体。

公开(公告)号：US5183749A

公开(公告)日：1993-02-02

申请号：US496183

申请日：1990-03-20

Applicant: Gerado Ramos ,  Oreste Ghisalba ,  Hans-Peter Schar ,  Bruno Frei ,  Peter Maienfisch ,  Anthony C. O'Sullivan

Inventor： Gerado Ramos ,  Oreste Ghisalba ,  Hans-Peter Schar ,  Bruno Frei ,  Peter Maienfisch ,  Anthony C. O'Sullivan

IPC: A01N49/00 ,  C07H19/01 ,  C12P17/18

CPC classification number: C07H19/01 ,  A01N49/00 ,  C12P17/181 ,  C12R1/525 ,  C12R1/685 ,  Y10S435/822 ,  Y10S435/886 ,  Y10S435/911 ,  Y10S435/917

Abstract: The present invention relates to a one-step microbial process for the preparation of 13.beta.-hydroxy- or 14,15-epoxy-milbemycins of the following formulae I and II ##STR1## in which R.sub.1 and R.sub.1 ' represent methyl, ethyl, isopropyl or sec.-butyl or represent the group ##STR2## in which X represents methyl, ethyl or isopropyl, and A and A' represent the group ##STR3## in which R.sub.2 represents hydrogen, --C(O)-CH.sub.2 O-C(O)-CH.sub.2 CH.sub.2 -COOH or --C(O)-CH.sub.2 CH.sub.2 -COOH, or mixtures of compounds of the formulae I and II, which process comprises bringing a milbemycin of the formula III ##STR4## dissolved in a liquid phase, in which R.sub.3 represents R.sub.1 or R.sub.1 ' and R.sub.4 represents A or A', and R.sub.1, R.sub.1 ', A and A' have the meanings given for formulae I and II, into contact with a microorganism that is capable of 13.beta.-hydroxylation or 14,15-epoxidation or of both reactions, or into contact with active constituents thereof. The microorganism or its active constituents may be either in free form or immobilized form.

Abstract translation: 本发明涉及一种用于制备下式I和II的13β-羟基或14,15-环氧 - 米尔倍霉素的一步微生物方法。其中R1 并且R 1'表示甲基，乙基，异丙基或仲丁基，或表示其中X表示甲基，乙基或异丙基的基团，A和A'表示其中R 2表示氢的基团，-C （O）-CH 2 O-C（O）-CH 2 CH 2 -COOH或-C（O）-CH 2 CH 2 -COOH，或式I和II化合物的混合物，该方法包括使式III的米尔倍霉素 III）溶解在液相中，其中R3表示R1或R1'，R4表示A或A'，R1，R1'，A和A'具有式I和II给出的含义，与微生物接触， 能够进行13β-羟基化或14,15-环氧化或两种反应，或与其活性成分接触。 微生物或其活性成分可以是游离形式或固定化形式。