Scalable Total Syntheses of N-Linked Tryptamine Dimers by Direct Indole−Aniline Coupling: Psychotrimine and Kapakahines B and F

摘要

Abstract: This report details the invention of a method to enable syntheses of psychotrimine (1) and thenkapakahines F and B (2, 3) on a gram scale and in a minimum number of steps. Mechanistic inquiries arenpresented for the key enabling quaternization of indole at the C3 position by electrophilic attack of annactivated aniline species. Excellent chemo-, regio-, and diastereoselectivities are observed for reactionsnwith o-iodoaniline, an indole cation equivalent. Additionally, the scope of this reaction is broad with respectnto the tryptamine and aniline components. The anti-cancer profiles of 1 3 have also been evaluated.