Enantioselective Biooxidation of Racemic <i>trans</i>‐Cyclic Vicinal Diols: One‐Pot Synthesis of Both Enantiopure (<i>S</i>,<i>S</i>)‐Cyclic Vicinal Diols and (<i>R</i>)‐α‐Hydroxy Ketones

Abstract

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 &gt;99% ee and ( S , S )‐cyclic diols in &gt;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 &gt;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 highly regio‐ and enantioselective oxidations of the racemic vicinal diols. magnified image