Stereoselective Synthesis of Maralixibat via VO(acac)2/Schiff Base-Catalyzed Asymmetric Oxidation of Its Sulfide Intermediate

Abstract

The stereoselective synthesis of maralixibat was achieved by harnessing the chiral transferring effect of the stereogenic R-sulfoxide functionality, which was obtained via the VO(acac)₂/Schiff base-catalyzed asymmetric oxidation of a phenylthiophenol prochiral intermediate. The R-sulfoxide intermediate underwent a ring closure reaction to form the seven-membered ring core structure with the desired stereochemistry, ultimately ensuring the drug’s exceptional isomeric purity and synthetic efficiency.