Total Synthesis of Trabectedin,Lurbinectedin,and Renieramycin T  

作　　者：Dong Li Jiaolong Meng Xuefeng Jiang 

机构地区：[1]Shanghai Key Laboratory of Green Chemistry and Chemical Process,East China Normal University,Shanghai 200062 [2]State Key Laboratory of Organometallic Chemistry,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 200032 [3]State Key Laboratory of Elemento-Organic Chemistry,Nankai University,Tianjin 300071

出　　处：《CCS Chemistry》2023年第9期2152-2158,共7页中国化学会会刊（英文）

基　　金：the financial support provided by National Science Foundation of China(grant nos.22125103 and 21971065);Science and Technology Commission of Shanghai Municipality(grant nos.22JC1401000,20XD1421500,and 20JC1416800).

摘　　要：Trabectedin and lurbinectedin are therapeutic antitumor pharmaceuticals approved by the Food and Drug Administration for treating soft tissue sarcomas and metastatic small cell lung cancer and have been facing synthesis challenges over the past three decades.In this report,the total synthesis of trabectedin,lurbinectedin,and renieramycin T were accomplished in 22-27 steps.The synthetic strategy features stereocontrolled Pictet-Spengler(PS)reaction leading to the multisubstituted tetrahydroisoquinoline fragment(DE ring),aldol condensation for C4-C10 bond formation,and a second PS cyclization with asymmetric oxomalonate for the fully substituted B ring,in which palladium complex-induced stereoselectivity is achieved via decarboxylative protonation anchoring the C1 stereocenter.The pentacyclic skeleton(A-E)was efficiently effectuated at a gramscale,displaying superior potential for further drug development.

关 键 词：TRABECTEDIN lurbinectedin renieramycin T total synthesis decarboxylative protonation 

分 类 号：O62[理学—有机化学]