A biocatalytic approach to the enantioselective synthesis of (R)- and (S)-malic acid

Abstract

(S)-Diethyl malate 1a was prepared (70–80% yield; > 98% optical purity) by an enantioselective reduction of sodium diethyl oxalacetate 2 by fermenting baker's yeast (Saccharomyces cerevisiae). Other microorganisms were tested for their capability of reducing 2. Most of them afforded (S)-1a-with ee from 8 to 94% and only Candida utilis, Aspergillus niger and Lactobacillus fermentum ILC G18D preferentially reduced compound 2 to (R)-1a. (R)-Dimethyl malate 1b was obtained from (R,S)-malate 1b by hydrolysis with pig liver esterase (PLE), the highest ee (93%) being realized at 0 °C in 20% aqueous methanol. Enzymatic hydrolyses of protected malates 1d and 1e did not lead to improvement of the ee.