Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

Hiroki Oguri, Haruki Mizoguchi, Hideaki Oikawa, Aki Ishiyama, Masato Iwatsuki, Kazuhiko Otoguro, Satoshi Ömura

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

By emulating the universal biosynthetic strategy, which employs modular assembly and divergent cyclizations, we have developed a four-step synthetic process to yield a collection of natural-product-inspired scaffolds. Modular assembly of building blocks onto a piperidine-based manifold 6, having a carboxylic acid group, was achieved through Ugi condensation, N-acetoacetylation and diazotransfer, leading to cyclization precursors. The rhodium-catalyzed tandem cyclization and divergent cycloaddition gave rise to tetracyclic and hexacyclic scaffolds by the appropriate choice of dipolarophiles installed at modules 3 and 4. A different piperidine-based manifold 15 bearing an amino group was successfully applied to demonstrate the flexibility and scope of the unified four-step process for the generation of structural diversity in the fused scaffolds. Evaluation of in vitro antitrypanosomal activities of the collections and preliminary structure - activity relationship (SAR) studies were also undertaken.

Original languageEnglish
Pages (from-to)930-940
Number of pages11
JournalBeilstein Journal of Organic Chemistry
Volume8
DOIs
Publication statusPublished - Jun 22 2012
Externally publishedYes

Fingerprint

Cyclization
Biological Products
Scaffolds
Bearings (structural)
Rhodium
Cycloaddition
Carboxylic Acids
Condensation
piperidine

Keywords

  • Chemical diversity
  • Divergent cyclization
  • Indole alkaloids
  • Modular assembly
  • Rhodium-catalyzed cyclization-cycloaddition
  • Skeletal and stereochemical diversity

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization. / Oguri, Hiroki; Mizoguchi, Haruki; Oikawa, Hideaki; Ishiyama, Aki; Iwatsuki, Masato; Otoguro, Kazuhiko; Ömura, Satoshi.

In: Beilstein Journal of Organic Chemistry, Vol. 8, 22.06.2012, p. 930-940.

Research output: Contribution to journalArticle

Oguri, Hiroki ; Mizoguchi, Haruki ; Oikawa, Hideaki ; Ishiyama, Aki ; Iwatsuki, Masato ; Otoguro, Kazuhiko ; Ömura, Satoshi. / Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization. In: Beilstein Journal of Organic Chemistry. 2012 ; Vol. 8. pp. 930-940.
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