Biogenetically inspired synthesis and skeletal diversification of indole alkaloids

Haruki Mizoguchi, Hideaki Oikawa, Hiroki Oguri

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

To access architecturally complex natural products, chemists usually devise a customized synthetic strategy for constructing a single target skeleton. In contrast, biosynthetic assembly lines often employ divergent intramolecular cyclizations of a polyunsaturated common intermediate to produce diverse arrays of scaffolds. With the aim of integrating such biogenetic strategies, we show the development of an artificial divergent assembly line generating unprecedented numbers of scaffold variations of terpenoid indole alkaloids. This approach not only allows practical access to multipotent intermediates, but also enables systematic diversification of skeletal, stereochemical and functional group properties without structural simplification of naturally occurring alkaloids. Three distinct modes of [4+2] cyclizations and two types of redox-mediated annulations provided divergent access to five skeletally distinct scaffolds involving iboga-, aspidosperma-, andranginine- and ngouniensine-type skeletons and a non-natural variant within six to nine steps from tryptamine. The efficiency of our approach was demonstrated by successful total syntheses of (±)-vincadifformine, (±)-andranginine and (-)-catharanthine.

Original languageEnglish
Pages (from-to)57-64
Number of pages8
JournalNature Chemistry
Volume6
Issue number1
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

Fingerprint

Indole Alkaloids
Alkaloids
Scaffolds
Cyclization
Secologanin Tryptamine Alkaloids
Biological Products
Functional groups
Structural properties
andranginine

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

Biogenetically inspired synthesis and skeletal diversification of indole alkaloids. / Mizoguchi, Haruki; Oikawa, Hideaki; Oguri, Hiroki.

In: Nature Chemistry, Vol. 6, No. 1, 01.01.2014, p. 57-64.

Research output: Contribution to journalArticle

Mizoguchi, Haruki ; Oikawa, Hideaki ; Oguri, Hiroki. / Biogenetically inspired synthesis and skeletal diversification of indole alkaloids. In: Nature Chemistry. 2014 ; Vol. 6, No. 1. pp. 57-64.
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