Synthesis of enantiopure (S)‐6‐chlorochroman‐4‐ol using whole‐cell Lactobacillus paracasei biotransformation

Abstract Chromane, which has a fused cyclic structure, is a significant molecule that can be found in the structure of many important compounds. Lactobacillus paracasei BD101 was demonstrated as whole‐cell biocatalyst for the synthesis of ( S )‐6‐chlorochroman‐4‐ol with immense enantioselectivity. The conditions of asymmetric reduction were optimized one factor by one factor using L paracasei BD101 to achieve enantiomerically pure product and complete conversion. Using these obtained optimization conditions, asymmetric reduction of 6‐chlorochroman‐4‐one was performed under environmentally friendly conditions; 6‐chlorochroman‐4‐one, having a fused cyclic structure as previously noted to be difficult to asymmetric reduction with biocatalysts, was enantiomerically reduced to ( S )‐6‐chlorochroman‐4‐ol with an enantiomeric excess >99% on a high gram scale. This study is the first example in the literature for the enantiopure synthesis of ( S )‐6‐chlorochroman‐4‐ol using a biocatalyst. Also notably, the optical purity of ( S )‐6‐chlorochroman‐4‐ol obtained in this study through asymmetric bioreduction using whole‐cell biocatalyst is the highest value in the literature. In this study, ( S )‐6‐chlorochroman‐4‐ol was produced on a gram scale by an easy, inexpensive, and environmentally friendly method, which has shown the production of valuable chiral precursors for drug synthesis and other industrial applications. This study provides a convenient method for the production of ( S )‐6‐chlorochroman‐4‐ol, which can meet the industrial green production demand of this chiral secondary alcohol.