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Synthesis of L‐histidine specifically labelled with stable isotopes

1994; Royal Netherlands Chemical Society; Volume: 113; Issue: 6 Linguagem: Inglês

10.1002/recl.19941130603

1878-7096

J. J. Cappon, K. D. Witters, J. Baart, Peter J. E. Verdegem, Aad Hoek, R. J. H. Luiten, Jan Raap, Johan Lugtenburg,

Fluorine in Organic Chemistry

Abstract (2′‐ 13 C)‐, (1′‐ 15 N)‐ and (3′‐ 15 N)‐L‐Histidine were prepared according to a synthetic scheme that allows the 13 C or 15 N 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, commercially available, highly enriched compounds. The labelled L‐histidines were characterized by mass spectrometry and 1 H‐, 13 C‐ and 15 N‐NMR spectroscopy.