Synthesis of Pandaroside D from via Construction of a Rare Enone System in the Steroid D Ring.

All marine saponins isolated from feature a unique and distinctive enone system located in the D ring and an unusual -C/D ring junction, presenting an intriguing yet unattained synthetic challenge. The first total synthesis of pandaroside D () and its methyl ester () was achieved from commercially available dehydroisoandrosterone acetate (DHEA). A notable feature of this synthesis is direct oxidation of the C-15 position promoted by the Davis reagent. This concept was applied despite the negative results of such an attempt described in the literature and confirmed the possibility of using the reagent in the direct construction of the enone system in ring D. For the final step, the reaction with sugar trichloroacetimidate proved unpromising; however, glycosylation of synthesized aglycone was successfully achieved using the classical Koenigs-Knorr variant with methyl 2,3,4-tri--acetyl-β-d-glucuronate bromide.