Concise Total Synthesis of Dysoxylactam A and a Simplified Analog  

作　　者：Guan-Zhou Yang Lei Wang Yao-Yue Fan Zeng-Wei Lai Xue-Ni Yu Li-Guang Lou Kun Gao Jian-Min Yue 

机构地区：[1]State Key Laboratory of Applied Organic Chemistry,College of Chemistry and Chemical Engineering,Lanzhou University,222 Tianshui South Road,Lanzhou,Gansu,730000 China [2]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,555 Zuchongzhi Road,Shanghai,201203 China [3]University of Chinese Academy of Sciences,No.19A Yuquan Road,Beijing,100049 China

出　　处：《Chinese Journal of Chemistry》2022年第17期2027-2034,共8页中国化学（英文版）

基　　金：support from the National Natural Science Foundation of China(Nos.81861138045,22177121);the CAMS Innovation Fund forMedical Sciences(2019-12M-5-080);the Biological Resources Program,CAS(KFJ-BRP-008-001)of People's Republicof China isgratefully acknowledged;support of Science and Technology Commission of Shanghai Municipality(20ZR1467800).

摘　　要：A total synthesis of 17-membered macrocyclolipopeptide dysoxylactam A,a potent agent reversing P-glycoprotein(P-gp)-mediated multidrug resistance(MDR)in cancer cells,was developed from the starting material(S)-2-methylbutanal in a linear sequence of 12 steps with 23.2%overall yield.The key steps include proline-catalyzed asymmetric aldol reaction,Evans aldol reaction and Krische allylation to construct the multiple stereocenters containing fragment,and ring-closing metathesis to furnish the macrocycle.This total synthesis facilitates the preparation of large amount samples of dysoxylactam A and the side chain simplified derivatives for further biological tests and preliminary structure-activity relationship exploration.

关 键 词：Total synthesis Dysoxylactam A Macrocyclolipopeptide Reversing multidrug resistance Structure-activity relationship 

分 类 号：O62[理学—有机化学]