Studies On Free-radical Promoted Synthesis Of Unnatural Amino Acids And Alkaloids

Polypeptides are a class of compounds formed by multiple amino acids,usually composed of 10-100 amino acid molecules.Polypeptides are ubiquitous in organisms.Up to now,tens of thousands of polypeptides have been found in organisms.They widely participate in and regulate the functional activities of various systems,organs,tissues and cells in the body,and play important roles in life.With the development of biotechnology and peptide synthesis technology,more and more peptide drugs have been developed and applied in clinic,which have been widely used in the prevention and treatment of cancer,diabetes,AIDS and other diseases due to their wide indications,high safety and significant curative effect.Therefore,researchers pay more and more attention to the chemical structure modification and synthesis of peptides and small molecular amino acids.The traditional synthesis and modification methods of small molecular peptides and amino acids are more dependent on transition metal catalysis,ligands and guide groups,or equivalent even large excess oxidants.Therefore,in order to develop a more greener and efficient method,we carried out the research work in this thesis.Through unremitting efforts,we have developed an effective access to unnatural α-amino acids.In addition,a new method of alkylation and acylation of N-heteroarenes has also been achieved.This thesis is divided into the following four parts.The first part of this chapter reviews the advances in synthesis of amino acids in recent years.And the second part summarizes the developments of alkylation using alcohol as the free radical precursor.Besides,the advantages and disadvantages of these methods are analyzed.In the second chapter,the author describes in detail the novel strategy for synthesis of unnatural α-amino acids developed by our research group.A variety of unnatural amino acids can be smoothly obtained by using aliphatic bronic acids as the alkyl source.And it only requires 1 atm of oxygen as the terminal oxidant,and any chemical oxidants,catalysts or additives are not needed.The author shares the process of optimizing reaction conditions,examination of substrate scope as well as the mechanistic studies.Furthermore the possible reaction mechanism is proposed.The third chapter detailed the new alkylation and acylation of N-heteroaromatics.And the discovery process and the characters of this approach is also demonstrated in details.The last part summarizes the two free-radical alkylation strategies we have developed,and puts forward the major innovations.Finally,the author makes a preliminary outlook for the future research direction in this area.