Highly diastereoselective total synthesis of Vibegron, a drug for overactive bladder disease

Abstract

A highly efficient and practical approach to the total synthesis of Vibegron, a drug for overactive bladder disease has been achieved through a substrate-directed diastereoselective reduction of ketone to syn-1,2-amino alcohol, enabling the synthesis of Vibegron in a highly stereoselective manner. Another key step involved in this approach is the formation of a cis-pyrrolidine ring via the sequential one-pot Pd/C-catalyzed olefin reduction, debenzylation, Cbz deprotection and reductive amination/cyclization. The total synthesis of Vibegron has been achieved in nine steps with an overall yield of 36 % starting from a readily available d-Serine. It is a non-enzymatic and alternate process to previous approaches.