Development of a Terpenoid Alkaloid-like Compound Library Based on the Humulene Skeleton

Haruhisa Kikuchi, Takehiro Nishimura, Eunsang Kwon, Junya Kawai, Yoshiteru Oshima

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Many natural terpenoid alkaloid conjugates show biological activity because their structures contain both sp3-rich terpenoid scaffolds and nitrogen-containing alkaloid scaffolds. However, their biosynthesis utilizes a limited set of compounds as sources of the terpenoid moiety. The production of terpenoid alkaloids containing various types of terpenoid moiety may provide useful, chemically diverse compound libraries for drug discovery. Herein, we report the construction of a library of terpenoid alkaloid-like compounds based on Lewis-acid-catalyzed transannulation of humulene diepoxide and subsequent sequential olefin metathesis. Cheminformatic analysis quantitatively showed that the synthesized terpenoid alkaloid-like compound library has a high level of three-dimensional-shape diversity. Extensive pharmacological screening of the library has led to the identification of promising compounds for the development of antihypolipidemic drugs. Therefore, the synthesis of terpenoid alkaloid-like compound libraries based on humulene is well suited to drug discovery. Synthesis of terpenoid alkaloid-like compounds based on several natural terpenoids is an effective strategy for producing chemically diverse libraries.

Original languageEnglish
Pages (from-to)15819-15825
Number of pages7
JournalChemistry - A European Journal
Volume22
Issue number44
DOIs
Publication statusPublished - 2016 Jan 1

Keywords

  • antihypolipidemics
  • chemical library
  • chemoinformatics
  • diversity-oriented synthesis
  • drug discovery
  • terpenoid alkaloids

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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