Institute of Chemistry, University of Campinas-UNICAMP, P.O. Box 6154, Campinas, SP 13083 970, Brazil.
Brazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, SP 13083-970, Brazil.
J Org Chem. 2022 Jun 17;87(12):7610-7617. doi: 10.1021/acs.joc.1c02952. Epub 2022 Feb 16.
Ellipticine was synthesized in six steps and 20% global yield starting from the readily available 2,5-dimethoxy isoquinoline. Unprecedented regioselective control of the nucleophilic attack on the isoquinoline-5,8-dione is first described. Investigation of the possible pathways of this transformation through density functional theory calculations reveals unexpected -oxide assistance in cascade tautomerizations, which was crucial for directing the nucleophilic attack and hastening the overall process. Using this strategy, we prepared the aniline-isoquinolinedione adduct and submitted it to an intramolecular double C-H cross-coupling activation to furnish ellipticinequinone, which gave ellipticine after a MeLi addition/BH reduction sequence.
从易得的 2,5-二甲氧基异喹啉出发，经过六步反应以 20%的总收率合成了椭圆碱。首次描述了对异喹啉-5,8-二酮上亲核进攻的前所未有的区域选择性控制。通过密度泛函理论计算研究了这种转化的可能途径，揭示了在级联互变异构中出人意料的 -氧化物辅助作用，这对于指导亲核进攻和加速整个过程至关重要。使用这种策略，我们制备了苯胺-异喹啉二酮加合物，并对其进行了分子内双 C-H 交叉偶联活化，得到了椭圆碱醌，经过 MeLi 添加/BH3 还原序列后得到了椭圆碱。
