Total Syntheses of Echitamine, Akuammiline, Rhazicine, and Pseudoakuammigine

Echitamine (1) and akuammiline (2) are representative members of a fascinating class of monoterpenoid indole alkaloids. We report the syntheses of 2 and its congener deacetylakuammiline (3). The azabicyclo[3.3.1]nonane motif was assembled through silver‐catalyzed internal alkyne cyclization, and one‐pot C−O bond cleavage/C−N bond formation furnished the pentacyclic scaffold. Compound 3 then served as a common intermediate for preparing a series of structurally diverse and synthetically challenging congeners including 1. A position‐selective Polonovski–Potier reaction followed by formal N‐4 migration built the core of N‐demethylechitamine (4) and 1. An alternative route featuring Meisenheimer rearrangement gave 4 as well. Oxidation of the alcohol within 3 gave rhazimal (5), which underwent tandem indolenine hydrolysis, hemiaminalization, and hemiketalization to form rhazicine (6). A sequence of N,O‐ketalization and reductive amination secured the chemoselectivity of N‐methylation, leading to pseudoakuammigine (7). Eines für alle: Kollektive Totalsynthesen von Echitamin, N‐Demethylechitamin, Akuammilin, Rhazimal, Rhazicin und Pseudoakuammigin wurden ausgehend von Deacetylakuammilin als gemeinsame Vorstufe entwickelt.