Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), Equipe MSMT, Univ. Paris-Sud, CNRS, Université Paris-Saclay, 15, rue Georges Clémenceau, 91405, Orsay, Cedex, France.
Pharmacognosie et chimie des substances naturelles, BioCIS, Univ. Paris-Sud, Université Paris-Saclay, CNRS, 92290, Châtenay-Malabry, France.
Angew Chem Int Ed Engl. 2018 Sep 17;57(38):12294-12298. doi: 10.1002/anie.201802610. Epub 2018 Apr 23.
We report the first total synthesis of (-)-17-nor-excelsinidine, a zwitterionic monoterpene indole alkaloid that displays an unusual N4-C16 connection. Inspired by the postulated biosynthesis, we explored an oxidative coupling approach from the geissoschizine framework to forge the key ammonium-acetate connection. Two strategies allowed us to achieve this goal, namely an intramolecular nucleophilic substitution on a 16-chlorolactam with the N4 nitrogen atom or a direct I -mediated N4-C16 oxidative coupling from the enolate of geissoschizine.
我们报告了 (-)-17-去甲蛇根碱的首次全合成，这是一种带有独特 N4-C16 连接的两性单萜吲哚生物碱。受假定生物合成的启发，我们探索了从金雀花堿骨架构建关键铵盐-乙酸盐连接的氧化偶联方法。有两种策略可以实现这一目标，即 16-氯内酰胺的 N4 氮原子的分子内亲核取代，或直接通过 I 介导的金雀花堿烯醇化物的 N4-C16 氧化偶联。
