Elucidation of the Structure of Pseudorubriflordilactone B by Chemical Synthesis

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.