Hans Georg Wilhelm Leuenberger

Screening for microorganisms performing the stereoselective reduction of α-formyl-esters

Summary107 Microorganisms selected from 26 genera belonging to bacteria, actinomycetes, fungi and yeasts were screened for their ability to reduce α-formyl-esters stereoselectively. Eighteen strains have been found which were able to reduce at least one of 5 substrates tested with an optical purity of more than 85% ee. The best strains were Candida humicola, Aspergillus petrakii, Streptomyces hydrogenans and Streptomyces griseus. The dependence of the enantioselectivity of the reduction on the group of microorganisms and on the substituents of the formyl-esters is discussed.

Asymmetric microbial reduction of ethyl and isoprophyl α,1,3-trioxo-2-isoindolinebutyrate

SummaryMicroorganisms are capable of the asymmetric reduction of various types of ketones. From a limited screening with 103 selected microbial strains two have been chosen which reduce ethyl and isopropyl α,1,3-trioxo-2-isoindolinebutyrate (1a and 1b) stereoselectively. The optically active products ethyl and isopropyl α-hydroxy-1,3-dioxo-2-isoindoline butyrate (2a and 2b) are useful precursors of the cerebral insufficiency improver hydroxy-aniracetam. Up to 3% of substrates 1a or 1b can be added in the reaction medium and converted by Candida parapsilosis. The isolated (R)-enantiomers of the product alcohols 2a and 2b show an enantiomeric excess (ee) of 98%–99%. The process was successfully tested on a 200-1 scale, the transformation rate being 0.83 g/1 per day and the yield of isolated product 72%. With Torulopsis magnoliae (S)-enantiomers of the products 2a and 2b were formed with an ee of 97%–99%.