Stereoselective microbial reduction of racemic acetyl(t-butyl)methylphenylsilane by Trigonopsis variabilis (DSM 70714) and Cornebacterium dioxydans (ATCC 2176)

Abstract

(Si R, C R)- and (Si S, C R)-t-butyl(1-hydroxyethyl)methylphenylsilane [(Si R, C R)- 2 and (Si S, C R)- 3] have been prepared by ( R)-selective microbial reduction fo racemic acetyl(t-butyl)methylphenylsilane ( rac- 1) using free cells of the yeast Trignopsis variabilis (DSM 70714) or the bacterium Corynebacterium dioxydans (ATCC 21766). The biotransformations were carried out on a 10 g scale. After the separation by column chromatography on silica gel, the optically active diastereonomers (Si R, C R)- 2 and (Si S, C R)- 3 produced by T. variabilis were obtained in good yields[74% ((Si R, C R)- 2, 78% ((Si S, C R)- 3]. The products obtained from the reduction with C. dioxydans were isolated in significantly lower yields [20% ((Si R, C R)- 2), 20% ((Si S, C R)- 3)]; reaction conditions not optimized). Both bioconversions gave products with high enantiomeric purities [ T. variabilis: 97% ee ((Si R, C R)- 2), 96% ee ((Si S, C R)- 3); C. dioxydans: ⪰ 99% ee ((Si R,C R)- 2), ⪰ 99% ee ((Si S, C R)- 3)]. To throw light on the stereochemical aspects of these biotransformations, an X-ray diffraction study was carried out on the 3,5-dinitrobenzoate of rac-(Si R, C S/(Si S, C R)- 3. In addition, 1H NMR spectroscopic stereochemical correlation studies were performed with the ( S)-MTPA esters derived from (Si R, C R)- 2, (Si S, C R)- 3, rac-(Si R, C R/(Si S, C S)- 2 and rac-(Si R, C S/Si S, C R)- 3 [ rac-(Si R, C R/Si S, C S)- 2 and rac-(Si R, C S/Si S, C R)- 3 were obtained by reduction of rac- 1 with LiAlH 4in diethyl ether, followed by chromatographic separation of the diastereonomers on silica gel]. These stereochemical studies allowed assignment of the absolute configurations and enantiomeric purities of the biotransformation products.