Preparation of 2-13C-L-Histidine Starting from 13C-Thiocyanate: Synthetic Access to Any Site-Directed Stable Isotope Enriched L-Histidine

摘要

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.