Total Synthesis of 1-O-Methyllateriflorone

摘要

With its unique spiroxalactone framework carrying a prenylated dihydrobenzoquinone moiety and a trioxatetracyclo[7.4.1.0~(2,7).0~(2.11)]tetradecane system, lateriflorone (1) represents an unusual synthetic challenge. Reported in 1999, this novel natural product was isolated from the stem bark of Garcinia Lterifora Bl (Guttiferae) collected from Indonesia, and it exhibits potent cytotoxicity against the P388 cancer cell line (ED_(50) = 5.4 μg mL~(-1)). Its seemingly fragile structure was secured by spectroscopic and X-ray crystallographic analysis. The secret of its stability, particularly at the siroxalactone-dihydroquinone junction, is probably due to the syn arrangement between the C2' proton and the C3' ester grouping which locks the leaving group in place, avoiding the β-elimination pathway that may lead to its rupture. The intriguing structural features of lateriforone, coupled with its biological activity, prompted us to seek a possible pathway for its construction in the laboratory. Herein we report our findings thus far in this project, including the first total synthesis of 1-O-methyllateriforone (2).