Regioselective domino metathesis of unsymmetrical 7-oxanorbornenes with electron-rich vinyl acetate toward biologically active glutamate analogues

Masato Oikawa*, Minoru Ikoma, Makoto Sasaki, Martin B. Gill, Geoffrey T. Swanson, Keiko Shimamoto, Ryuichi Sakai

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

In this article a regioselective domino metathesis reaction of unsymmetrical 7-oxanorbornenes, readily available by a tandem Ugi/Diels-Alder reaction as a key step, promoted by the Hoveyda-Grubbs second-generation catalyst in the presence of electron-rich vinyl acetate as a cross metathesis (CM) substrate is reported. The mechanism for the unusually high regioselectivity observed in the CM reaction was investigated, and a reaction course where a Fischer-type carbene ["Ru" = CH(OAc)] generates a steric interaction is proposed. The metathesis products were further converted to four artificial glutamate analogues whose structures were inspired by naturally derived excitatory glutamate analogues, dysiherbaine and neodysiherbaine. Interestingly, one of the synthetic analogues (28a) induced a cataleptic state in mice. Further electrophysiological studies suggest that 28a might inhibit excitatory synaptic transmission by a yet unknown indirect pathway.

Original languageEnglish (US)
Pages (from-to)5531-5548
Number of pages18
JournalEuropean Journal of Organic Chemistry
Issue number32
DOIs
StatePublished - 2009

Keywords

  • Carbenes
  • Combinatorial chemistry
  • Domino reactions
  • Glutamate analogues
  • Metathesis
  • Regioselectivity

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

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