Antimony salt-promoted cyclization facilitating on-DNA syntheses of dihydroquinazolinone derivatives and its applications  

作　　者：Qigui Nie Jie Sun Xianfu Fang Xun He Feng Xiong Gong Zhang Yangfeng Li Yizhou Li 

机构地区：[1]Chongqing Key Laboratory of Natural Product Synthesis and Drug Research,Innovative Drug Research Center,School of Pharmaceutical Sciences,Chongqing University,Chongqing 401331,China [2]Shenzhen Innovation Center for Small Molecule Drug Discovery Co.,Ltd.,Shenzhen 518110,China [3]Chemical Biology Research Center,School of Pharmaceutical Sciences,Chongqing University,Chongqing 401331,China [4]Key Laboratory of Biorheological Science and Technology,Ministry of Education,College of Bioengineering,Chongqing University,Chongqing 400044,China [5]Beijing National Laboratory for Molecular Sciences,Beijing 100190,China

出　　处：《Chinese Chemical Letters》2023年第8期201-207,共7页中国化学快报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(Nos.22222702,22107016,22107017 and 21907011);the Fundamental Research Funds for the Central Universities(No.2022CDJQY-001);Beijing National Laboratory for Molecular Sciences(No.BNLMS202104);the Natural Science Foundation of Chongqing(Nos.cstc2020jcyj-jqX0009,cstc2021jcyjmsxmX0016 and cstc2021jcyj-cxttX0002);High-end Foreign Expert Introduction Program(No.G2022165020L);Shenzhen Innovation Center for Small Molecule Drug Discovery Co.(No.H20220687).

摘　　要：DNA-encoded chemical libraries technology has become a novel approach to finding hit compounds in early drug discovery.The chemical space in a DEL would be expanded to realize its full potential,especially when integrating privileged scaffold dihydroquinazoline that has demonstrated a variety of diverse bioactivities.Driven by the requirement of parallel combinatorial synthesis,we here report a facile synthesis of on-DNA dihydroquinazolinone from aldehyde and anthranilamide.This DNA-compatible reaction was promoted by antimony trichloride,which has been proven to accelerate the reaction and improve conversions.Notably,the broad substrate scope of aldehydes and anthranilamides was explored under the mild reaction condition to achieve moderate-to-excellent conversion yields.We further applied the reaction into on-DNA macrocyclization,obtaining macrocycles embedded dihydroquinazolinone scaffold in synthetically useful conversion yields.

关 键 词：DNA-encoded chemical libraries ANTIMONY Dihydroquinazolinone MACROCYCLIZATION DNA-compatible chemistry 

分 类 号：TQ460.1[化学工程—制药化工]