Asymmetric Total Synthesis of (+)-Epiibogamine Enabled by Three-Component Domino Michael/Michael/Mannich Annulation of N‑Sulfinyl Metallosilylenamines

The iboga alkaloids are promising antiaddictive and neuroregeneration candidates for medical treatment. There is a lack of studies for C20-epi iboga alkaloids due to the synthetic difficulties. Herein we report the shortest total synthesis of (+)-epiibogamine in seven steps from trimethyl orthobutyr...

Full description

Saved in:
Bibliographic Details
Published inOrganic letters Vol. 25; no. 6; pp. 956 - 960
Main Authors Yu, Po-Cheng, Karmakar, Anupam, Sabbers, William A., Shajan, Femil, Andrade, Rodrigo B.
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 17.02.2023
Online AccessGet full text

Cover

More Information
Summary:The iboga alkaloids are promising antiaddictive and neuroregeneration candidates for medical treatment. There is a lack of studies for C20-epi iboga alkaloids due to the synthetic difficulties. Herein we report the shortest total synthesis of (+)-epiibogamine in seven steps from trimethyl orthobutyrate. The novel N-sulfinyl silylenamine reagent enabled the key step, with three-component domino Michael/Michael/Mannich annulation providing the 1-amino-2,4-diester scaffold with four new chiral centers, and access to the isoquinuclidine in high yield (84%) and diastereoselectivity (>95:5 dr).
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1523-7060
1523-7052
DOI:10.1021/acs.orglett.2c04287