Palladium-Catalyzed Carbonylative Transformations of Bromhexine into Bioactive Compounds as Glucocerebrosidase Inhibitors

摘要

A general synthesis for dicarbonylated derivatives of the parent drug bromhexine is described. By using the commercially available Pd(OAc)_2/BuPAd_2 (CataCXium A, Ad = adamantyl) catalyst system, the carbonylative arylation, amination, and alkoxylation of bromhexine proceeded with up to 79% product yield. Selected synthesized derivatives of bromhexine showed improved effects as glucocerebrosidase inhibitors.