Development of an Efficient and Scalable Biocatalytic Route to (1S,4R)-8-Hydroxy-1,2,3,4- tetrahydro-1,4-methanonaphthalen-5-yl Propionate via Enantioselective Enzymatic Desymmetrization of a Prochiral Diester

An efficient procedure for enzymatic desymmetrization of the prochiral diphenol compound 2 was successfully developed to prepare the pharmaceutical intermediate (1S,4R)-8-hydroxy-1,2,3,4-tetrahydro-1,4-methanonaphthalen-5-yl propionate with 99.0% purity and 97.82% ee in 81.59% overall yield. The enzymatic reaction was scalable and cost-effective and avoided the process of crystallization-induced resolution in the reported synthetic strategy for yimitasvir (1), thus helping to increase utilization of the chiral motif.