A STUDY OF BAKERS-YEAST REDUCTION OF PIPERIDONE-CARBOXYLATES

The stereoselective baker's yeast reduction of various N-protected pip eridone-carboxylic acids have been studied, and the enantioselectivity was found to be widely dependent on whether fermenting or non-ferment ing conditions were employed. Thus reaction of N-tert-butoxycarbonyl-4 -oxopiperidine-3-carboxylic acid ethyl eater (6) with fermenting baker 's yeast gave almost racemic rt-butoxycarbonyl-4-hydroxypiperidine-3-c arboxylic acid ethyl ester (7), however, with complete diastereoselect ivity. Reduction of 6 with non-fermenting yeast gave 7 with a 24-41% e nantiomeric excess. Similarly, reduction of N-tert-butoxycarbonyl-3-ox opiperidine-4-carboxylic acid ethyl ester (17) with fermenting baker's yeast gave racemic rt-butoxycarbonyl-3-hydroxypiperidine-4-carboxylic acid ethyl ester [(+/-)-18] diastereoselectively. A convenient method for determining the enantiomeric excess of the hydroxypiperidine carb oxylic acids derivatives was found in the reaction with Sanger's reage nt followed by HPLC on a chiral column.