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[摘要]：Two epoxide-contg. peptidomimetics I and II of the isopeptide glutamyl-g-glutamate have been synthesized via a route that should be generally applicable to the synthesis of isopeptide analogs in which an oxirane replaces the scissile peptide bond. Enzymes that catalyze the hydrolysis of peptides and isopeptides are often susceptible to inactivation by electrophilic substrate analogs. In this research, an epoxide was installed as an electrophilic replacement of the scissile isopeptide bond. The C-terminal glutamyl mimic was accessed by the stereospecific synthesis of suitably substituted cyclopentenes III and IV as surrogates for either the L- or D- enantiomer. The enantiomeric cyclopentenes were further elaborated to incorporate an appended sulfone that was reacted with a suitably protected glutamyl-g-semialdehyde in a Julia-Kocienski olefination reaction. This olefination afforded predominantly the desired E-olefin isosteres of L-glutamyl-g-D-glutamate and L-glutamyl-g-L-glutamate, following which peracid-mediated epoxidn. and deprotection provided I and II. |
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