Total Synthesis Of Natural Oligostilbenes And Methodology Research

Resveratrol oligomers,polymerized with stilbene ramifications,have widely drawn attention in research field due to their significant bioactivities.After years of research done by our staff room,it was found that Resveratrol oligomers,such as Pallidol(7),had weak estrogenic and anti-estrogenic activities,and might become a promising therapeutic agent for ERT,just like isoflavnones.The research on this topic has never been reported yet.Due to the scarcity of resveratrol oligomers from natural sources,the demand of the research and clinical application couldn't be met only through the extraction from natural plants.So there is of significance in performing the total synthesis of this kind of products.Our group has achieved an accessible route to make Pallidol(7) and its analogs.But it still has its disadvantages like too much steps and low yields of products.Besides,there occurred two interesting phenomenon that need to be explored clearly.The task of this dissertation was designed to simplify the former synthesis route, obtain the four natural products,such as Isopaucifloral F(6) and Quadrangularin A(5), and develop the methodology research on some interesting reactions.At first,3,5-dimethoxybenzoic acid 11 was selected as the starting material,and was made into compound 14 through three step reactions.After we compared different methods,BBr₃ was chosen on the Demethylating reaction of methyl ethers. Then we successfully achieved the natural product Isopaucifloral F(6).Next,on the base of our group's former research achievements,we designed to start the simplification work from compound 14,and completed the addition of 4-methoxybenzyl fragment onto it through a one-step-reaction instead of the former five-step-ones.Our strategy is based on the reference report,through which we overcame the ketone's enolization problem under alkalescent condition in nucleophilic addition by use of TiCl₄.In this thesis,we have worked on the nucleophilic addition on compound 14 with Grignard agent in TiCl₄ solvent,and succeeded the template reaction in which the methyl or benzyl fragment was introduced onto 14.The foundation of this method made it possible to introduce fragment we want onto the target compound,and laid a better ground for the further simplification research as well.What's more,we developed methodology research to explore two interesting reactions within the synthesis route,and have achieved some progress as follow:1.We successfully developed a new and convenient synthetic method of stilbenes, in which benzils and arylmethyldiphenylphosphine oxides were used to form stilbenes bearing electron-withdrawing group(s) stereoselectively via Wittig-Horner reaction and a rearrangement in the presence of t-BuOK in toluene under mild conditions and in high yield.This is the first time to report that benzyls can be used to synthesize stilbenes through this approach.It could be readily applied to a facile synthesis of biologically important natural products,resveratrol and its derivatives.2.We founded the method to synthesize kinetic product cis-diarylinden-1-one 14' and thermodynamic product trans—diarylinden-1-one 14 through Nazarov cyclization under mild condition.We explored the relationship among the substituent effect,reaction speed and the stereochemical outcome to give the clear mechanism of the whole process from cyclization to the epimerization of cis-isomer to trans-isomer,in which the electron-donating groups at arenes and the steric hinderness of the substituent at theβpostion played important roles.