One-Pot Evolution of Ageladine A through a Bio-Inspired Cascade towards Selective Modulators of Neuronal Differentiation

Takayuki Iwata, Satoshi Otsuka, Kazuki Tsubokura, Almira Kurbangalieva, Daisuke Arai, Koichi Fukase, Youichi Nakao, Katsunori Tanaka

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

A bio-inspired cascade reaction has been developed for the construction of the marine natural product ageladine A and a de novo array of its N1-substituted derivatives. This cascade features a 2-aminoimidazole formation that is modeled after an arginine post-translational modification and an aza-electrocyclization. It can be effectively carried out in a one-pot procedure from simple anilines or guanidines, leading to structural analogues of ageladine A that had been otherwise synthetically inaccessible. We found that some compounds out of this structurally novel library show a significant activity in modulating the neural differentiation. Namely, these compounds selectively activate or inhibit the differentiation of neural stem cells to neurons, while being negligible in the differentiation to astrocytes. This study represents a successful case in which the native biofunction of a natural product could be altered by structural modifications.

Original languageEnglish
Pages (from-to)14707-14716
Number of pages10
JournalChemistry - A European Journal
Volume22
Issue number41
DOIs
Publication statusPublished - 2016

Keywords

  • 2-aminoimidazole
  • ageladine A
  • natural products
  • neural differentiation
  • one-pot synthesis

ASJC Scopus subject areas

  • Chemistry(all)

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