Screening, substrate specificity and stereoselectivity of yeast strains, which reduce sterically hindered isopropyl ketones

Towards the synthesis of sterically hindered optically active secondary alcohol 2, yeast strains (Candida floricola IAM 13115 and Trichosporon cutaneum IAM 12206) with si-face hydride attack on isopropyl phenylsulfonylmethyl ketone 1 were developed by screening. Strains with complementary re-facial selectivity (Pichia angusta IAM 12895 and Pichia minuta IAM 12215) were also found. Based on the substrate specificity studies of these four strains, microbial reduction was applied to the synthesis of (3S,5S)-2,6-dimethyl-3,5-heptanediol 12a.

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(R)-3-Methyl-1-phenylsulfonyl-2-butanolC11H16O3SEe = 94.0%[α]D20=-16.7 (c 0.98, EtOH)Source of chirality: Trichosporon cutaneum-catalyzed asymmetric reductionAbsolute configuration: (R)

(S)-3-Methyl-1-phenylsulfonyl-2-butanolC11H16O3SEe = 96.8%[α]D22=+18.0 (c 0.97, EtOH)Source of chirality: Pichia minuta-catalyzed asymmetric reductionAbsolute configuration: (S)

(3S,5S)-2,6-Dimethyl-3,5-heptanediolC9H20O2Ee = 100%[α]D22=-64.3 (c 1.01, MeOH)Source of chirality: Candida floricola-catalyzed asymmetric reduction and Pseudomonas cepacia lipase-catalyzed kinetic resolutionAbsolute configuration: (3S,5S)