Hughes Alexander J, Townsend Steven D
Department of Chemistry, Vanderbilt University, Nashville, TN 37235, United States.
European J Org Chem. 2024 Aug 12;27(30). doi: 10.1002/ejoc.202400442. Epub 2024 Apr 26.
We describe the first total syntheses of tabernanthine and ibogaline. Entry to these iboga alkaloid natural products is enabled by a thermal coupling of indoles and aziridines to furnish the requisite nosyl tryptamine starting materials. This route features a Friedel-Crafts type alkylation to form the key indole-isoquinuclidine C-C bond. Finally, a regio- and diastereoselective hydroboration-oxidation enables C-N bond formation to close the isoquinuclidine ring system and deliver tabernanthine and ibogaline in 10 and 14% yield respectively. Both syntheses were completed in eight steps.
我们报道了士的宁碱和伊博格碱的首次全合成。通过吲哚与氮丙啶的热偶联来制备这些伊博格生物碱天然产物所需的对甲苯磺酰色胺起始原料。该路线的特点是通过傅克型烷基化反应形成关键的吲哚 - 异喹核碱碳 - 碳键。最后，区域和非对映选择性硼氢化 - 氧化反应实现碳 - 氮键的形成，从而闭合异喹核碱环系，分别以10%和14%的产率得到士的宁碱和伊博格碱。两种合成均在八步反应中完成。
