Studies On Photocatalytic DNA Compatible C3 Alkylation Of Quinoxalin-2(1H)-ones

DNA-encoded library(DEL)technology is an emerging screening method and powerful tool for discovering target ligands in chemical biology research and new drug development.Quinoxalinones,especially C3-functionalized derivatives have proved as an important scaffold of N-containing heterocycles in a wide range of natural products and biologically active compounds.The functional development of the C3 position of quinoxalinone and the construction of a compound library containing the dominant skeleton of quinoxalinone have great research value and broad application prospects.In the field of construction of C-C bond at C3 position of quinoxalinone,the photocatalytic reaction has achieved fruitful results due to its mild conditions,green,and high efficiency.This paper reviews the research status of DEL,quinoxalinone and photochemistry,aiming to introduce photochemistry into DEL synthesis,using the advantages of DEL technology and combining the quinoxalinone structure core with a wide range of biological activities to develop a method for constructing libraries of quinoxalinone compounds,providing effective strategies for discovering new target ligands from natural-sourced compounds.In this paper,we designed a specific experimental program for the development of a photocatalytic-based functionalization method at the C3 position of quinoxalinone using DNA encoding technology.Based on the visible light-induced decarboxylation coupling reaction,using amino acids and acids as alkyl radical donors,we have successfully developed two gentle methods that can directly and regioselectively perform alkylation for quinoxalinone compounds by investigating various experimental parameters involved in the reaction,and a series of DNA-encoded quinoxalinone C3 alkylated products have been obtained with medium and high yields.This article also carried out the substrates scope study,and the results showed that the two alkylation schemes developed have a wide range of free radical sources of amino acids and organic acids,and the reaction conditions are all applicable to the 7 quinoxalinone analogues with different substituent groups used in the article,which has a wide range of applications;In this paper,the amplifiable rate of DNA was determined by q PCR test,and the damage of the two strategies developed to the DNA sequence responsible for encoding was evaluated.And the experimental results show that the two experimentally developed photocatalytic decarboxylation coupling schemes have good to better stability and readability to the DNA chain responsible for information encoding(97% and 69% respectively),which provides a feasible basis for constructing a library of DNA-encoded quinoxalinone compounds.