Photoinduced C(sp~3)-H Alkylation Under Catalyst-free Conditions And Its Application In Peptide Synthesis

Peptides usually refer to compounds formed by dehydration and condensation of 10-100 amino acid molecules,which are widely distributed and play an important role in life.Peptide drugs regulate many important life activities mainly by interacting with proteins.They have the advantages of high affinity and low toxicity to target.However,there are many shortcomings in these drugs,such as poor metabolic stability and short half-life,which hinder the clinical application of polypeptide drugs.Some chemical modification methods can improve the disadvantages of the above polypeptide drugs.It mainly includes: chemical modification of peptide chain or introduction of polymer,site-directed mutation or modification of amino acid sequence.The construction of C-C bonds is an important research field in organic synthesis and an indispensable technical support for the construction of drug molecules in drug synthesis.Functionalization of C-H bond is one of the most direct methods to construct C-C bond.Previous organic reactions mainly regulate the chemical selectivity of different functional groups.However,the functionalization of C-H bond can only occur regioselective reaction of target C-H bond through specific means,even in the presence of other functional groups with higher reactivity.Introducing a specific aliphatic group into a molecule usually results in significant changes in the biological characteristics and pharmacological activities of the target molecule.There have been many reports on the photocatalysis catalyzed by transition metals or organic photosensitizers,but the development of photocrosslinking reaction without catalyst is slow.A method for the construction of non-natural amino acids from glycine derivatives and alkyl iodine without catalysis is reported.In this study,we investigated the effects of reactant concentration,time,illumination intensity and illumination time on the reaction,and obtained the best reaction conditions.Under these optimum conditions,the compatibility of substrates was systematically investigated.The experimental results show that the first,second and third alkyl iodides have good reaction effects.In addition,glycine esters,glycine amides,alpha-aminone,N-aryl tetrahydroisoquinoline and polypeptide molecules can be selectively alkylated under standard conditions.Finally,on the basis of the reaction results,we propose a possible reaction mechanism.