Elucidation of the Structure of Pseudorubriflordilactone B by Chemical Synthesis

Abstract

Rubriflordilactone B (1) is a schinortriterpenoid isolated by Sun and colleagues, which possesses a tetrasubstituted benzene moiety and eight stereocenters. The previous synthesis of 1 by Li and co-workers uncovered the existence of its naturally occurring stereoisomer “pseudorubriflordilactone B”. Here we report a collaborative study by the two groups that elucidates the structure of pseudorubriflordilactone B to be 16,17-bis-epi-rubriflordilactone B (26). Chemical synthesis served as an important tool in the structure determination. Taking advantage of a modular synthetic route, we systematically “mutated” the configurations of C-23, C-22, C-20, and C-16/C-17 located at the right-hand domain of 1, and thus prepared its 15 stereoisomers for spectrum comparison. The 1H NMR spectra of synthetic 26 in deuterated chloroform and pyridine were identical to those of authentic pseudorubriflordilactone B, respectively. This synthetic sample displayed anti-HIV activity (EC50 = 0.288 μM) in vitro.