The State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Nano-Micro Materials Research, School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen 518055, China.
The State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China.
J Am Chem Soc. 2022 Aug 10;144(31):14396-14402. doi: 10.1021/jacs.2c06518. Epub 2022 Jul 27.
The first asymmetric total synthesis of (+)-alstonlarsine A has been realized. The prominent features of the current synthesis include the following: (i) a Pd/self-adaptable ligand complex-catalyzed asymmetric allylic alkylation of 2-methyl-2-cyclopentenyl carbonate with 2-indolylsubstituted dimethyl malonate to establish the key stereocenter of C15, (ii) an intramolecular nitrile oxide-alkene [3 + 2] cycloaddition (INOC [3 + 2]) to construct the cyclohepta[]indole backbone with the installment of the requisite stereochemistry of the all-carbon quaternary center of C20, and (iii) a late-stage Pictet-Spengler reaction (IPSR) to rapidly assemble the core structure of (+)-alstonlarsine A.
已实现 (+)-alstonlarsine A 的首次不对称全合成。当前合成的突出特点包括：（i）Pd/自适性配体配合物催化 2-甲基-2-环戊烯基碳酸酯与 2-吲哚取代的二甲基丙二酸二甲酯的不对称烯丙基烷基化，以建立 C15 的关键立体中心，（ii）分子内腈氧化物-烯烃 [3 + 2] 环加成（INOC [3 + 2]），以构建具有所需的 C20 全碳季碳原子的立体化学的环庚[]吲哚骨架，和（iii）晚期Pictet-Spengler 反应（IPSR），以快速组装（+）-alstonlarsine A 的核心结构。
