Ciba-geigy Corporation

Sankyo Company, Limited

Hans-Peter Schar

Oreste Ghisalba

Peter Maienfisch

Anthony Cornelius O'Sullivan

Gottfried Sedelmeier

Bruno Frei

Daniel Gygax

Rente Lattmann

Gerado Ramos

Elke Schmidt

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.

Microbial process for the preparation of milbemycin derivatives

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.

Process for the preparation of hydroxy acids

Growing community of inventors

Aesch, Switzerland

Hans-Peter Schar