Kloeckera corticis ATCC

Enantioselective reduction of the prochiral cyclic acylsilane 42 with growing cells of the yeast Kloeckera corticis (ATCC 20109) yielded the optically active reduction product (R)-43 (Scheme 8)53. On a preparative scale, the l-silacyclohexan-2-ol (R)-43 was isolated in 60% yield with an enantiomeric purity of 92% ee. Repeated recrystallization of the biotransformation product from n-hexane raised the enantiomeric purity to 99% ee. 

Analogous enantioselective biotransformations have been achieved with the silicon compounds 217 and 219, which were transformed into the respective optically active products (S)-218 (yield 90%, enantiomeric purity 84% ee) and (S)-220 (yield 80%, enantiomeric purity 76% ee) using growing cells of Kloeckera corticis (ATCC 20109)278,279. Particularly remarkable is the conversion of the hydridosilane 219 which could be performed without a noticeable degree of hydrolytic cleavage of the Si-H bond (incubation conditions pH 5.5, 27 °C). 

All biotransformations mentioned above represent enantioselective reductions. In contrast, the reduction of the cyclic chiral acylsilane vac-225 with growing cells of Kloeckera corticis (ATCC 20109) into a 1 1 mixture of (S,R)-226 and (jR,S)-226 is an example of a diastereoselective conversion (yield of reduction product 95%, diaster-eomeric excess 90% de)19,283. 

Summary rac-l-(4-Fluorophenyl)-l-methyl-l-sila-2-cyclohexanone (rac-1) and rac-(SiS, C/ /Sii ,CS)-2-acetoxy-l-(4-fluorophenyl)-l-methyl-l-silacycIohexane [rac-(Si5,Ci /Siiil,C5)-3a] were synthesized as substrates for stereoselective microbial transformations. Resting free cells of the yeast Saccharomyces cerevisiae (DSM 11285) and growing cells of the yeasts Trigonopsis variabilis (DSM 70714) and Kloeckera corticis (ATCC 20109) were found to reduce rac- diastereoselectively to yield mixtures of the enantiomers (S S,CR)- and (SLR,C5)-l-(4-fluorophenyl)-l-methyl-1-sila-2-cyclohexanol [(Si5,C/ )-2a and (SLR,CS)-2a]. In the case of Kloeckera corticis (ATCC 20109), diastereoselective reduction of rac-1 gave a quasi-racemic mixture of (Si5,CR)-2a and (SiR,CS)-2a (diastereomeric purity 95 % de, yield 95 %). Enantioselective ester hydrolysis (kinetic resolution) of the 2-acetoxy-l-silacyclohexane rac-(Si5,CR/Si/ ,C5)-3a yielded the optically active l-sila-2-cyclohexanol (Si/ ,C5)-2a [enantiomeric purity >99% ee yield 56 % (relative to (Si, C5)-3a)]. 

The l-sila-2-cyclohexanone rac-1 was found to be reduced diastereoselectively by resting free cells of Saccharomyces cerevisiae (DSM 11285) and by growing cells of Trigonopsis variabilis (DSM 70714) and Kloeckera corticis (ATCC 20109) to give mixtures of the enantiomeric l-sila-2-cyclo-hexanols (Si5, C/ )-2a and (Si/f,C5)-2a as the major products (Scheme 2). 

The best preparative results were obtained with Kloeckera corticis (ATCC 20109). Reduction of rac- with growing cells of this particular microorganism yielded a 1 1 mixture of (Si5, CR)-2a and (Si/ ,CS)-2a in 95 % yield the diastereomeric purity of the product was 95 % de. 

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