- Preparation of 2'-13c-l-histidine starting from 13c-thiocyanate: Synthetic access to any site-directed stable isotope enriched l-histidine
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1-Benzyl-2-(methylthio)-imidazole-5-ketone is obtained in a few simple steps starting from thiocyanate and glycine amide (glycin). Subsequent treatment with diethyl phosphorocyanidate and functional group manipulations gives 1-benzyl-5-chloromethylimidazolium chloride. This compound is converted under mild O'Donnell conditions into the corresponding L-histidine derivative. After deprotection L-histidine is obtained in good yield and 99% enantiomeric excess. 2'-13C-L-Histidine has been obtained via this new scheme with high (99%) 13C incorporation starting with commercially available 13C- thiocyanate. This synthetic scheme allows access to any isotopomer of L-histidine and many other biologically important imidazole derivatives.
- Talab, Sarra,Taha, Kamal Khalifa,Lugtenburg, Johan
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p. 1023 - 1033
(2014/02/14)
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- Synthesis of L-histidine specifically labelled with stable isotopes
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(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.
- Cappon, J. J.,Witters, K. D.,Baart, J.,Verdegem, P. J. E.,Hoek, A. C.,et al.
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p. 318 - 328
(2007/10/02)
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