1. Synthetic Studies On The Derivatives Of Saucernetin-8, An Inhibitor Of HIF-1α 2. Total Synthesis Of (-)-Talaumidin And (-)-Galbelgin

Synthetic studies on the derivatives of Saucernetin-8,an inhibitor of HIF-1αSaucernetin-8,functionally unique dineolignans,was isolated from active root extracts of Saururus cernuus L and found to be a potent inhibitor of the transcription factor HIF-1α.In order to further investigate the structure-activity relationships,we designed and synthesized several new tetrahydrofuran and adamantan derivatives,based on the lead compound Saucernetin-8.Structures of all synthesized products were confirmed by ¹H NMR,MS.All of these researches have great value for the further study on the SAR.Total synthesis of(-)-Talaumidin and(-)-Galbelgin(-)-Talaumidin and(-)-galbelgin are naturally occurring lignans isolated from Aristolochia arcuata and Piper futokadsura.The two compounds were proved to have significant neurotrophic property in the primary culture of rat cortical neurons,and could serve as a promising lead compound for treatment of neurodegenerative disorders,such as Alzheimer's and Parkinson's disease.In this thesis full details are showed for the total synthesis of(-)-talaumidin and(-)-galbelgin,by using 4-pentenoic acid as starting material with the overall yield about 17.8%and 16.9%.The key steps include asymmetry Aldol reaction,TBS protection,Hydroboration reduction,NaIO₄ oxidation,Friedel-Crafts arylation,etc.The structures of the target compounds were determined by ¹H-NMR,¹³C-NMR,MS.The data was consistant with that of the natural product, (-)-talaumidin and(-)-galbelgin published in the literature.