Total Synthesis and Structure Revision of (+)-Lancilactone C

Abstract

Lancilactone C is a tricyclic triterpenoid that inhibits human immunodeficiency virus (HIV) replication in H9 lymphocytes with no cytotoxicity. Its tricyclic skeleton comprises trans-dimethylbicyclo[4.3.0]nonane and 7-isopropylenecyclohepta-1,3,5-triene. The latter unique structure, in which all carbon atoms are sp 2 hybridized, is not found in other triterpenoids and needs to be verified synthetically. Herein, we have accomplished the first total synthesis of lancilactone C (proposed structure) by developing a new domino [4 + 3] cycloaddition reaction involving oxidation, Diels−Alder reaction, elimination, and electrocyclization. We have also revised the structure based on the total synthesis of lancilactone C according to its plausible biosynthetic pathway.L ancilactone C was isolated from the stems and roots of Kadsura lancilimba, which have been traditionally used in Chinese folk medicine, along with lancilactones A, B, and kadsulactone A while searching for potential anti-HIV agents (Figure 1). 1 Its structure, including relative stereochemistry,