Enantioselective biooxidation of racemic trans-cyclic vicinal diols: One-pot synthesis of both enantiopure (S,S)-cyclic vicinal diols and (R)-α-hydroxy ketones

Abstract

Highly regio- and enantioselective alcohol dehydrogenases BDHA (2,3-butanediol dehydrogenase from Bacillus subtilis BGSC1A1), CDDHPm (cyclic diol dehydrogenase from Pseudomonas medocina TA5), and CDDHRh (cyclic diol dehydrogenase from Rhodococcus sp. Moj-3449) were discovered for the oxidation of racemic trans-cyclic vicinal diols. Recombinant Escherichia coli expressing BDHA was engineered as an efficient whole-cell biocatalyst for the oxidation of (±)-1,2-cyclopentanediol, 1,2-cyclohexanediol, 1,2-cycloheptane-diol, and 1,2-cyclooctanediol, respectively, to give the corresponding (R)-α-hydroxy ketones in >99% ee and (S,S)-cyclic diols in >99% ee at 50% conversion in one pot. Escherichia coli (BDHA-LDH) co-expressing lactate dehydrogenase (LDH) for intracellular regeneration of NAD+ catalyzed the regio- and enantioselective oxidation of (±)-1,2-dihydroxy-1,2,3,4- tetrahydronaphthalene to produce the corresponding (R)-α-hydroxy ketone in >99% ee and (S,S)-cyclic diol in 96% ee at 49% conversion. Preparative biotransformations were also demonstrated. Thus, a novel and useful method for the one-pot synthesis of both vicinal diols and α-hydroxy ketones in high ee was developed via high Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.