title: Regioselective Domino Metathesis of Unsymmetrical 7-Oxanorbornenes with Electron-Rich Vinyl Acetate toward Biologically Active Glutamate Analogues.
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.
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama 236-0027, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Oikawa
authors.forename: Minoru
authors.initials: M
authors.lastname: Ikoma
authors.forename: Makoto
authors.initials: M
authors.lastname: Sasaki
authors.forename: Martin B
authors.initials: MB
authors.lastname: Gill
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Swanson
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimamoto
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Sakai