Selective Modification Of Polypeptide Alkyl Side Chains Based On Free Radical Strategy

Peptide chemistry not only plays an important role in the development of modern pharmaceutical industry,but also greatly promotes the development of life science and chemistry.Polypeptides are a class of compounds composed of amino acids linked by peptide bonds,which are important active substances in the formation of life and play an important role in life.For example,they can be used as an agonist for signal transduction and regulate the signal transduction process in cells.Many successful peptide drugs also have the same effect.Peptide drugs have attracted extensive attention due to their good biological activity and biocompatibility.However,due to the limited structure of natural amino acids,the natural peptides composed of them often have low biological activity and drug activity,which seriously restricts the rapid development of polypeptide drugs.Due to their structural diversity and reproducibility,non-natural amino acids have attracted much attention in the synthesis of novel functional non-natural peptides.Therefore,the development of efficient,simple and rapid direct modification of polypeptide to produce structural and property changes is of vital importance in the field of organic synthetic chemistry,chemical biology and pharmaceutical chemistry,and is also one of the most challenging research topics.In this paper,the amino acids containing aliphatic side-chain were used as the research object,and the selective modification of aliphatic side-chain in amino acids and polypeptides was realized by using the radical policy,which was mainly divided into the following two parts:In the first part,aliphatic amino acids modified by azofluorosulfonamide were studied.Under the catalysis of Cupric acetylacetonate,the aliphatic amino acids were conjugated with disulfide compounds to obtain the thioetherification products at the ?position of the aliphatic side-chain of amino acids,thus realizing the directional modification of different amino acid derivatives.This method has the characteristics of wide application range of substrates,good compatibility of functional groups,and good applicability to complex intermediates with potential biological activity,which highlights its unique synthesis potential.In the second part,the precise modification of the aliphatic side-chain at the Nterminal of the peptide was realized by selective halogenation of N-H bond at the terminal of the peptide and subsequivuent cyclization.The method requivuires only visible light and base,and the reaction conditions are simple.High amino acid compatibility,can be compatible with 13 kinds of natural amino acids.Dipeptides,tripeptides,tetrapeptides and pentapeptides all showed good reaction efficiency and selectivity under this reaction condition.