Abstract

Racemic and enantioselective synthesis of tetrahydroprotoberberine (THPB) alkaloids, a family of natural products showing a wide range of biological activity, have been based either on extension or enhancement of conventional methods or on new, recently developed tactics. Classical approaches to synthesize the THPB scaffold have utilized Bischler-Napieralski cyclization/reduction or Pictet-Spengler reactions to generate a benzyltetrahydroisoquinoline motif, followed by Mannich type condensation to obtain the tetracyclic THPB core. In recent developments, contiguously tetra-substituted ring D moieties and chiral auxiliaries to install the chiral center have been utilized to synthesize THPBs. The present review summarizes various approaches adopted to synthesize THPBs and their congeners, based on the sequence of formation of rings B and C.

Keywords: THPB, tetrahydroprotoberberine, stepholidine, tetrahydropalmatine, chiral auxiliary, isocorypalmine, stylopine, govadine.

Graphical Abstract