Reduction of phenylalkyl ketones to the corresponding (S)-hydroxy derivatives using mucor hiemalis IFO 5834

DETAILED DESCRIPTION OF THE INVENTION In one aspect, the present invention provides a stereoselective process for reducing a phenylalkyl ketone to the corresponding (S)-hydroxy derivative, which comprises contacting said phenylalkyl ketone with Mucor hiemalis.
In a preferred embodiment said phenylalkyl ketone has the formula (III): ##STR3## and said (S)-hydroxy derivative has the formula (IV): ##STR4## wherein R.
sup.
1 is hydrogen, halogen, lower alkyl, lower alkoxy, CO.
sub.
2 R.
sup.
5, COR.
sup.
5 or C(R.
sup.
6).
sub.
2 --O--R.
sup.
7 ; or a radical of the formula: ##STR5## R.
sup.
2 is hydrogen, halogen, lower alkyl, lower alkoxy, CO.
sub.
2 R.
sup.
5, COR.
sup.
5 or C(R.
sup.
6).
sub.
2 --O--R.
sup.
7 ; R.
sup.
3 and R.
sup.
4 are independently hydrogen or halogen; and R.
sup.
5 is hydrogen or lower alkyl; R.
sup.
6 is lower alkyl; and R.
sup.
7 is hydrogen or a hydroxy protecting group.
A is --CH.
dbd.
CH--S-- or --CH.
dbd.
CH--CH.
dbd.
CH--; n is 1 to 3.
In a more preferred embodiment, said phenylalkyl ketone has the formula (IIIa): ##STR6## wherein R.
sup.
2 is CO.
sub.
2 R.
sup.
5 or C(R.
sup.
6).
sub.
2 --O--R.
sup.
7 ; R.
sup.
3 is hydrogen and R.
sup.
4 is chlorine; or R.
sup.
3 and R.
sup.
4 each is fluorine; R.
sup.
5 is hydrogen or lower alkyl; R.
sup.
6 is lower alkyl; and R.
sup.
7 is hydrogen or a hydroxy protecting group.
More preferably, in compounds of formulae (IIIa) and (IVa) R.
sup.
3 is hydrogen and R.
sup.
4 is chlorine; R.
sup.
2 is CO.
sub.
2 R.
sup.
5 ; and R.
sup.
5 is methyl.
Abbreviations and Definitions In the application, unless specifically stated otherwise, the following abbreviations and definitions apply.
FAB-MS=fast atom bombardment mass spectrometry HPLC=high pressure liquid chromatography MES=N-morpholinoethanesulfonic acid NMR=nuclear magnetic resonance TLC=thin-layer chromatography UV=ultraviolet "Alkyl" includes linear, branched and cyclic structures and combinations thereof.
"Lower alkyl" means alkyl groups of from 1 to 7 carbon atoms.
Examples of lower alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, s- and t-butyl, pentyl, hexyl, heptyl, cyclopropyl, cyclobutyl, cyclopentylmethyl, cyclohexyl, and the like