Enantioselective synthesis of vicinal diols by an enzymatic approach

Chiral vicinal diols are crucial scaffolds frequently used for the preparation of adrenomimetic drugs. Biotransformation of benzaldehyde is one of the most effective strategies to access chiral vicinal diol. Herein, we present a novel and ecofriendly biocatalytic approach for synthesizing vicinal diol in good yield (>97%) and excellent ee (>97%). This method involves employing HeBAL, a benzaldehyde lyase from Herbiconiux sp. SALV-R1, as a catalyst for the crucial benzoin condensation step in synthesizing a ketone precursor. The treatment of benzaldehyde with BAL, in the presence of thiamin-diphosphate (ThDP) and Mg2+, results in the formation of alpha-hydroxy ketone, which subsequently undergoes biotransformation by carbonyl reductases (CR) to yield vicinal diols as the final product. The mutation of HeBAL highlights the pivotal role played by two specific alanine amino acid residues, Ala(392) and Ala(476). Furthermore, the catalysis by HeBAL effectively eliminates the formation of self-condensation by-products, which holds great implications for future phenylephrine synthesis.