Preparation of halohydrin beta-blocker precursors using yeast-catalysed reduction

The preparation of halohydrin beta -blocker precursors using yeast-catalyse d reduction of alpha -haloketones was performed. The influence in the yield and e.e, of several process variables was analysed. The (S)-enantioselecti vity observed with Saccharomyces cerevisiae can be changed to (R)-enantiose lectivity using methyl vinyl ketone as selective inhibitor (25 mM). Using r esting fresh cells better yields and e.e.s are observed than using growing cells. Yarrowia lipolytica 1240 resting cells gave 87% yield of (S)-1-chlor o-3(1-naphthyloxy)propan-2-ol (99% e.e.). Pichia mexicana 11105 resting cel ls gave 85% yield of (R)-1-chloro-3(1-naphthyloxy)propan-2-ol (precursor of propranolol) (95% e.e). The reduction process is applied to other alpha -h aloketones, a lower e.e, being obtained the closer the size of the ketone s ubstituents. (C) 2001 Elsevier Science Ltd. All rights reserved.