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Total Syntheses of Echitamine, Akuammiline, Rhazicine, and Pseudoakuammigine
Author(s) -
Zhang Xiang,
Kakde Badrinath N.,
Guo Rui,
Yadav Sonyabapu,
Gu Yucheng,
Li Ang
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201901086
Subject(s) - chemistry , chemoselectivity , stereochemistry , reductive amination , nonane , amination , hydrolysis , alkyne , combinatorial chemistry , organic chemistry , catalysis
Abstract 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 ).