Enzymatic approach to the synthesis of chiral intermediate of Rodatristat ethyl

Ketoreductases are widely explored for the reduction of prochiral ketones for the preparation of chiral alcohols. Though, the chiral Ir(III) catalyst has been used for the asymmetric reduction of keto intermediate of Rodatristat ethyl, an enzymatic approach for its preparation has not yet been reported. In this regard, we report, for the first time the preparation of enantiopure secondary alcohols (R-3) and (S-3) from 1-(5-chloro-[1,1'-biphenyl]-2-yl)-2,2,2-trifluoroenthan-1-one (2) using commercially available ketoreductases at 30 C-degrees in the presence of 125 mM sodium phosphate buffer pH 6 over 24 h. This enzymatic approach provides the (R)-3 and (S)-3 chiral alcohols in >99% enantiomeric excess (ee) with >99% conversion using KRED-244 and KRED-101 respectively. Furthermore, the KRED-244 and KRED-101 enzymes have been successfully immobilized with sodium alginate, which makes them recyclable and reusable in subsequent reactions. The reusability experiments were carried out over 15 cycles without any apparent loss of activity even after 10 cycles. It is a sustainable approach to the synthesis of enantiopure intermediates of rodatristat ethyl, contributing to the advancement of green chemistry. [GRAPHICAL ABSTRACT]