Trigonopsis variabilis DSM

Studies with resting free cells of Trigonopsis variabilis (DSM 70714) demonstrated that the enantiomeric purity of (R)-41 depends significantly on the substrate concentration... 

By analogy with the stereoselective microbial reduction of the acetylsilane rac-48 (Scheme 10) and its derivatives rac-51, rac-54 and rac-57, the related acetyldisilane rac- 60 was also found to be reduced (R)-selectively with resting free cells of Trigonopsis variabilis (DSM 70714) to give a 1 1 mixture of the corresponding diastereomeric... 

Growing cells of Trigonopsis variabilis (DSM 70714) were found to reduce the acyclic chiral acetylsilane vac-111 enantioselectively to give the diastereomeric optically active (l-hydroxyethyl)silanes (R,R)-228 and (S,R)-228 (yield of reduction product 50%, enantiomeric purity 90 [(R,R)-228] and 94% ee [(S,R)-228], respectively)285,286. Both the yield and the enantiomeric purity of the products could be significantly improved by using resting free cells (yield 74%, enantiomeric purity of both diastereomers 96% ee substrate concentration 0.35 g/1, 37 °C)282. The optically active silanes (R,R)-228 and (SyR)-118 can be separated by chromatography on silica gel without a noticeable decrease in yield. 

By analogy to the biotransformation of rac-221, the structurally related acetyldisilane rac-229 and the acetylsilane rac-231 were also reduced enantioselectively using resting free cells of Trigonopsis variabilis (DSM 70714)282,287. The conversion of rac-229 leads to a mixture of the optically active disilanes (R,R)-230 and (S,R)-230 (yield 75%, enantiomeric purity of both diastereomers >98% ee) and the transformation of rac-231 leads to a mixture of the optically active silanes (R,R)-232 and (S,R)-232 (yield 72%, enantiomeric purity of both diastereomers 94% ee). These reactions were carried out at 37 (rac-229) and 44 °C (rac-231), respectively the substrate concentrations used were 0.53 g/1. Especially remarkable is the biotransformation of the disilane rac-229 which could be realized without a noticeable degree of hydrolytic cleavage of the Si-Si bond. 

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). 

A number of reductive biotransformations of acyl silanes into a-hydroxy silanes have appeared recently. Acetyl dimethylphenylsilane is converted into (/f)-(l-hydroxyethyl) dimethylphenylsUane by plant cell suspension cultures of Symphytum officinale L. and Ruta graveolens L. in low yields but in 81% ee and 6% ee, respectively . SUanol and disUoxane were observed as by-products. Microbial reduction of racemic acetyl t-butyldimethylsilane has been achieved using Trigonopsis variabilis (DSM 70714) and Corynebacterium dioxydans (ATCC 21766) on a 10- gramme scale with > 96% ee in each case and in up to 78% yield . Recently, Saccharomyces cerevisiae (DHWS 3), a commercially available form of bakers yeast, has been shown to reduce acetyl dimethylphenylsilane, again to (/ )-(1-hydroxyethyl) dimethylphenylsilane, in 40% yield and >99.5% ee . 

---