Synthesis of L-histidine specifically labelled with stable isotopes

Article abstract of DOI:10.1002/recl.19941130603

(2'-13C)-, (1'-15N)- and (3'-15N)-L-Histidine were prepared according to a synthetic scheme that allows the 13C or 15N labelling of all carbon and nitrogen positions or any combination of positions.A 1,5-disubstituted imidazole ring was constructed via condensation of tosylmethyl isocyanide with 3-phenylpropenal and subsequent cycloaddition of benzylamine.The imidazole intermediate was converted into 1-benzyl-5-(chloromethyl)-imidazolium chloride which was coupled to a glycine moiety via an enantioselective coupling with the bislactim ether of cyclo-D-valylglycine.Deprotection of the coupling product afforded L-histidine in high optical purity.Syntheses for the isotopically labelled synthons were developed starting from simple, comercially available, highly enriched compounds.The labelled L-histidines were characterized by mass spectrometry and 1H-, 13C- and 15N-NMR spectroscopy.