Abstract
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-chloromethyl-imidazolium 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.
Highlights
L-Histidine constitutes a unique amino acid residue in peptides and proteins
The access to a whole library of side directed stable isotope-enriched histidine is essential to study the role of histidine in the proteins which are responsible for respiration and photosynthesis at the atomic level with isotope sensitive techniques without perturbation [3]
In this paper we describe the synthesis of 2'-13C-L-histidine (1a) via a new scheme that allows access to any isotopologue and isotopomer of L-histidine
Summary
L-Histidine constitutes a unique amino acid residue in peptides and proteins. Its pKa value is in the range of 6.4–7.0, so histidine residues account to a large extent for the buffer capacity of the protein system [1]. The access to a whole library of side directed stable isotope-enriched histidine is essential to study the role of histidine in the proteins which are responsible for respiration and photosynthesis at the atomic level with isotope sensitive techniques without perturbation [3]. This deeper level of knowledge obtained in this way is essential to get a fundamental understanding of these important life processes. In the present scheme the O’Donnell asymmetric amino acid synthesis is used, allowing mild reaction conditions and simple workups [4]. Benzyl isothiocyanate is formed in a simple reaction between potassium thiocyanate and benzyl chloride
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