Development of an artificial assembly line generating skeletally diverse indole alkaloids inspired by biogenetic strategy

Haruki Mizoguchi, Hiroki Oguri

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

With intention to formulate a potentially general synthetic strategy generating a collection of skeletally diverse scaffolds without simplifying a structural feature of natural products, we devised an artificial assembly line of terpenoid indole alkaloids and its variants. Inspired by the key biosynthetic intermediate, dehydrosecodine, responsible for divergent intramolecular cyclizations, a "multipotent intermediate" with improved stability and versatile reactivity was designed to establish a streamlined divergent synthetic process. A newly developed copper-catalyzed cyclization protocol allowed rapid formation of the sensitive dihydropyridine system. By harnessing the versatile reactivity of the multipotent intermediate, three types of bioinspired [4+2] cycloadditions as well as two types of oxidation-triggered cyclizations were successfully implemented to generate five distinct scaffolds involving iboga-, aspidosperma-, and ranginine- and ngouniensine-type skeletons and unnatural tetracyclic framework within 6-9 steps from tryptamine. Furthermore, simple manipulations of the [4+2] products allowed total synthesis of (-)-catharanthine, (±)-vincadifformine and (±)-andranginine, demonstrating a structural relevance of our compound collections to the natural products.

Original languageEnglish
Pages (from-to)854-865
Number of pages12
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume74
Issue number9
DOIs
Publication statusPublished - Jan 1 2016
Externally publishedYes

Fingerprint

Indole Alkaloids
Cyclization
Biological Products
Scaffolds
Secologanin Tryptamine Alkaloids
Cycloaddition
Copper
Oxidation

Keywords

  • Biomimetic synthesis
  • Dihydropyridine
  • Indole alkaloid
  • Multipotent intermediate
  • Skeletal diversity

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

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