The Synthesis And Structural Modification Of Novel Natural Product-Selaginellin L

So far, the screened mGluR5 antagonists were designed either on the basis of the CADD (Aided Drug Design) or from the compound library directly. Until now, there was no report concerning the mGluR5 antagonist from the natural products. Selaginellin, which has a new carbon scaffold, was first isolated from the Selaginella sinensis in 2007 by Zhang Li-ping et al. (Lan Zhou University). Afterwards, our research group has successfully isolated a serial of 12 derivatives of Selaginellin. According to prophase bioactivity experiment with Selaginellin, and analysis of the related reference, we speculated the Selaginellin L perhaps is the natural antagonist of mGluR5.In this study, it is the first time to take the natural product-Selaginellin L as the lead compound to design and synthesize the mGluR5 antagonist. Through the chemical reactions:Bromination, Suzuki, Sonogashira and Diazotization, etc., we successfully synthesized the target compounds--ND--selaginellin 13 and MPEPa 9. The structures were confirmed by the modern spectrum technology. In addition, this study explored the synthesis routes of the related compounds. We designed three synthesis routes for the compound 9, and successfully complete the route 3; and we designed two synthesis routes for compound 17, and successfully complete these two routes. In addition, we explored some important chemical reaction, such as bromination, Suzuki, Sonogashira reactions, ect., in the field of medicine, chemical industry, and found a optimal method of preparation. Meanwhile, with fluorine boron salt as substrate in the Suzuki reaction, we found a novel carbon chain extension method.