The Synthesis Of Velcade Analogues And Design,synthesis, Application In Steglich Rearrangement Of Bifunctional Organic Catalysts With DMAP As Scaffold

Study on stoichiometric asymmetric synthesis and catalytic asymmetric reaction has become a focus of organic chemistry. Especially, the synthesis of enantiomerically pure compounds, design of new catalyst, new finding of reaction and new concept of catalysis have made remarkable progress.Velcade can bring survival benefits to Multiple myeloma and a non-Hodgkin’s lymphoma patients as a proteasome inhibitor. However, many shortcomings need to be overcome urgently in the process of treatment.Chiral thiourea catalysts have attracted considerable attention due to their easy preparation, strong structure adaptability, good hydrogen bond donor. Notably, design, synthesis and their application in asymmetric reactions of bifunctional thiourea catalysts gain more passion.In this work, we synthesized a serial of Velcade analogues, chiral bifunctional catalysts bearing multiple hydrogen bond donors with DMAP as scaffold and catalytic properties of bifunctional catalyst were explored tentatively. The research consists mainly of three parts:In the first chapter, we reviewed recent study on the construction of chiral molecular and the research progress of asymmetric catalytic reactions, listing some representative catalysts, reaction types and the modes of catalysis.In the second chapter, some aminoxy acids, which were finally converted into Velcade analogues, were synthesized taking natural amino acid as raw material.In the third chapter, a serial of bifunctional catalysts with DMAP as scaffold were developed taking4-Cl-pyriding as raw material. The catalytic performance of the catalysts was detected in the Steglich rearrangement reaction. It is shown that the reaction can transformed quantitively and high selectivity can be obtained up to80%ee under the optimized system with only5%catalyst loading in dry toluene.