Stereospecific microbial reduction of ethyl 1-benzyl-3-oxo-piperidine-4-carboxylate

Microbial reduction of ethyl 1-benzyl-3-oxo-piperidine-4-carboxylate by the majority of evaluated microorganisms gave the ethyl cis-(3R,4R)-1-benzyl-3R-hydroxy-piperidine-4R-carboxylate as the major product in high diastereo- and enantioselectivities. The 3R,4R-hydroxy ester was produced in 97.4% diastereomeric excess (de) and 99.8% enantiomeric excess (ee) by Candida parapsilosis SC16347, while 99.5% de and 98.2% ee were obtained from reduction by Pichia methanolica SC16415. A few of the evaluated microorganisms gave 10–40% of the ethyl trans-(3R,4S)-1-benzyl-3R-hydroxy-piperidine-4S-carboxylate as the minor product.

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Ethyl cis-(3R,4R)-1-benzyl-3-hydroxy-piperidine-4-carboxylateC15H21NO3Ee = 99.3%De = 99.5%[α]D = +48.4 (c 2.35, CHCl3)Source of chirality: microbial reductionAbsolute configuration: (3R,4R)

Ethyl trans-(3R,4S)-1-benzyl-3-hydroxy-piperidine-4-carboxylateC15H21NO3Ee = 99.5%De = 96%[α]D = +23.6 (c 1.68, CHCl3)Source of chirality: microbial reductionAbsolute configuration: (3R,4S)