Design,Synthesis And Application Of Novel Coupling Reagent NDTP And Catalyst Cat-se For Peptide Synthesis

Amide is one of the most basic functional groups in organic chemistry,which is widely present in various natural products,materials and drugs.It’s also the core unit of peptides and proteins.In the past 30 years,the amidation reaction has always been the most frequently used reaction in the field of pharmaceutical chemistry.At present,the use of excessive coupling reagents is the main way to synthesize amide directly in industry,but it causes a lot of waste at the same time.The sustainable development of amide or peptide formation has been one of the major challenges in green chemistry since 2006.The main way to solve this problem is to develop cheaper,safer,more efficient and more atom economy coupling reagents and catalysts.In the dissertation,the research progress of direct synthetic amides was summarized at first(chapter 1).Then the coupling reagent NDTP(Chapter 2)and the catalyst Cat-Se(Chapter 3)were designed respectively based on previous work,and they were successfully applied to the synthesis of amides and peptides.Compared with various reported coupling reagents and catalysts,they all showed unique advantages and powerful application potential.In the coupling reagent section,we know that the traditional acyl halide reagents are often irritating and prone to product racemization in use,which limits their application in amides synthesis,especially in peptide synthesis.In order to solve the above problems,we had developed the reagent NDTP.It’s a mild and efficient coupling reagent,which was developed based on acyl halide,with a pyrimidine ring as the skeleton.It could convert carboxylic acids and amines into corresponding amides in 1 minute,and without racemization.In addition,the by-products formed by NDTP could be recovered by simple filtration,chlorination and thiocyanation,which also showed its better atom economy.More importantly,NDTP solved the problem of racemization due to oxazolonation in peptide synthesis than the reported acyl halide reagents.In the catalyst section,although some breakthroughs have been made in this field in the past 20 years,most of these studies have used reaction conditions that are not attractive in applications such as water removal,high temperature and gas protection.In addition,long reaction time and expensive catalysts are also unattractive.To solve the above problems,we designed the catalyst Cat-Se,which had simple structure and easy to synthesis.It could quickly convert carboxylic acids and amines into corresponding amides in high yield without racemization,and the process didn’t require water removal or gas protection.The reaction could be carried out under various conditions,such as room temperature,heating and lighting.Compared with the reported catalysts,it avoided many disadvantages which were unfavorable to industrialization.In short,it’s a catalyst with comprehensive advantages.More surprisingly,both NDTP and Cat-Se could be used for solid phase peptide synthesis,which provided new solutions for sustainable synthesis research of amides and peptides.Finally,the dissertation summed up the achievements of the above research,and made a further prospect for the later work.