A Study In The Total Synthesis Of 8', 8''-Demethyl Manassantin-8

Manassantin-A, a member of the tetrahydrofuran lignans, was first seperated from Saururus cernuus. It is a very good inhibitor of hypoxia-inducible factor 1α(HIF-1α).The total synthesis of Manassantin-A that reported was completed by over 20 steps with poor yield so it could not match the needs of drug research. In order to have a primary study in the structure-activity relationship of Manassantin-A, and to propose new good selectively anti-cancer drugs based on it, this thesis design and synthesize the racemic 8',8''-demethyl Manassantin-A. Using 2-methoxyphenol as starting material, followed by bromation, TBS protection, Weinreb ketone synthesis, then reduction, cyclation, deprotection of TBS, connect with the side chain and finally reduction, the synthesis is completed in 12 steps. The stucture of the product is confirmed by 1H NMR and MS. Futhermore, the theoretical study of the synthetic method of the optically active 8',8''-demethyl Manassantin-A and early works of it's synthetic practices are also described in the last part of this thesis.