Asymmetric reductions of ethyl 2-(benzamidomethyl)-3-oxobutanoate by yeasts

The stereoselective reduction of ethyl 2-(benzamidomethyl)-3-oxobutanoate 1 using yeasts was investigated among a restricted number (12) of yeasts. Kluyveromyces marxianusvar.lactis CL69 diastereoselectively produced (2R,3S)-ethyl 2-(benzamidomethyl)-3-hydroxybutanoate 2, whereas Pichia glucozyma CBS 5766 gave (2S,3S)-2 as the major stereoisomer. The biotransformations were independently optimized for minimizing by-product formation and maximizing the diastereoselectivity. Under optimized conditions, K. marxianus var. lactis CL 69 gave the (2R,3S)-ethyl 2-(benzamidomethyl)-3-hydroxybutanoate 2 with ee > 99% and de = 98%, while P. glucozyma CBS 5766 allowed for the production of (2S,3S)-2 with ee > 99% and de = 86%.

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(R)-N-(3-Hydroxybutyl)benzamideC11H15NO2[α]D25=-13.7 (c 0.28, CHCl3)Absolute configuration: (R)

(2R,3S)-Ethyl 2-(benzamidomethyl)-3- hydroxybutanoateC14H19NO4[α]D25=-49.7 (c 0.14, CHCl3)Absolute configuration: (2R,3S)