Total Synthesis Of Hapalosin And Studies On Total Synthesis Of Nemonapride

With the gradual depletion of land resources and deteriorating environment for human survival, people advocate the concept of sustainable development and maintain the ecological balance of the system has become a major issue related to human survival and development.Ocean covers a vast area, the vast expanse of ocean pregnant with infinite resources, from the ocean to find natural products have become an important physiological activity of the moment biologists, chemists and pharmaceutical workers of research. At the same time as people in-depth study of the phenomenon of life is different from ordinary human biological discovery, most natural products have important physiological activity does not directly interact with human proteins.Diversity synthesis of natural products is a direct source of drug discovery, and its final destination is found in drug molecules can function in the human body. To be able to effectively act on the biological macromolecules new target-oriented, to build natural product compound libraries has become an important part of natural products chemistry.Therefore, a new method based on modern organic synthesis, the importance of new technology to carry out important physiological activity of natural product synthesis for further reveal the diversity of natural products and biological interactions, the development of new drugs used to combat a variety of diseases have improved the quality of life.This work mainly focus our great efforts on the methodology of the cyclic peptide alkaloids Hapalosin which can inhibit multidrug resistance,and also the molecular(2S,3S)-Nemonapride which is an antipsychotics.The main results are as follows:1、 The group has built a new method to synthesis the compound 198.And by ring-opening, protection,methylation of 198,the hydroxy amino acids 200 can easily be obtained.2、 Through the reaction induced by the Evans cofactor,a non-pepetide fragment stereochemiistry 175 has been built.And then by the condensation reaction thesynthesis of 208 pieces has been completed.3 、 Having finished the docking of the compound 200 and 208 through the esterfication,then make the reaction of amidation by intramolecular to achieve the Hapalosin,which is a inhibitor of multi-drug resistance cyclic peptide alkaloids.4、Staring from D-malic acid,the imine compound 196 can be obtained by 6 steps reactions.A new method of synthesis 4-OTBS-5-methyl pyrrol amide compound 238 a has been developed, which is based on the reaction between magnesium bromide and imine compound 196 induced by co-ortho OTBS chiral group with high selectivity.By condensation and azide those seven-steps reactions,the good selective synthesis method of antipsychotics(2S,3S)-Nemonapride has been established with 17% overall yield.