Synthesis of Isopeptide Epoxide Peptidomimetics

Autor:	Matthew D Alexander, Debatosh Majumdar, James K. Coward
Rok vydání:	2008
Předmět:	Ethylene Oxide chemistry.chemical_classification Isopeptide bond Peptidomimetic Stereochemistry Organic Chemistry Epoxide Stereoisomerism Alkenes Article Sulfone chemistry.chemical_compound Stereospecificity chemistry Biomimetic Materials Electrophile Epoxy Compounds Peptide bond Enantiomer
Zdroj:	The Journal of Organic Chemistry. 74:617-627
ISSN:	1520-6904 0022-3263
DOI:	10.1021/jo801907p
Popis:	Two epoxide-containing peptidomimetics of the isopeptide, glutamyl-gamma-glutamate, have been synthesized via a route that should be generally applicable to the synthesis of isopeptide analogues 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 analogues. 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, 8 and 10, 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-gamma-semialdehyde in a Julia-Kocienski olefination reaction. This olefination afforded predominantly the desired E-olefin isosteres of L-glutamyl-gamma-D-glutamate and L-glutamyl-gamma-L-glutamate, following which peracid-mediated epoxidation and deprotection provided the epoxide-containing peptidomimetics, 4 and 5.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8f7eab055a3e09cda177817b85275b9f https://doi.org/10.1021/jo801907p Zobrazit plný text záznamu