文献类型：期刊文献

英文题名：Total Synthesis of Scholarisines A, I, T, and W and Identification of Scholarisine I as a Lysosome Inhibitor

作者：Guo, Rui[1];Li, Fan[1];Wang, Lin[2];Ba, Mengyu[1];Guo, Zhicong[1];He, Weiwei[2];Li, Ang[1]

机构：[1]Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Chem Biol, Shanghai 200032, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China

年份：2026

卷号：148

期号：26

起止页码：27023

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;Scopus(收录号：2-s2.0-105044806496);WOS:【SCI-EXPANDED(收录号:WOS:001804328600001)】；

基金：This work is dedicated to the memory of Prof. Amos Smith. We thank Jingyi Huang, Kosuke Minagawa, and Dr. Jason Chen for discussions. This work was supported by National Natural Science Foundation of China (21931014, 22477026, and U24A20807), Chinese Academy of Sciences (XDB1060000, YSBR-095, and XBZG-ZDSYS-202303), and Science and Technology Commission of Shanghai Municipality (JCYJ-SHFY-2022-005 and 25ZR1402564). A.L. is grateful to the New Cornerstone Science Foundation for the Xplorer Prize.

语种：英文

摘要：Scholarisine A (1) represents a structurally distinct and synthetically intriguing subfamily of the echitamine/akuammiline-type alkaloids. Inspired by its postulated biogenetic logic, we developed a radical cyclization strategy that retains the key bond-forming site while replacing the aldol reaction. This reaction-altering biomimetic strategy, combined with expeditious preparation of a tetracyclic precursor, enabled a 13-step, scalable synthesis of 1. Moreover, facile access to its congeners, scholarisines I, T, and W (2-4), was achieved. Compound 2 impairs lysosomal degradative capacity and thus inhibits late-stage autophagy in cancer cells.