Preparation of 2'-13C-L-histidine starting from 13C-thiocyanate: synthetic access to any site-directed stable isotope enriched L-histidine

Sarra Talab; Kamal Khalifa Taha; Johan Lugtenburg

doi:10.3390/molecules19011023

Preparation of 2'-13C-L-histidine starting from 13C-thiocyanate: synthetic access to any site-directed stable isotope enriched L-histidine

Molecules. 2014 Jan 15;19(1):1023-33. doi: 10.3390/molecules19011023.

Authors

Sarra Talab¹, Kamal Khalifa Taha², Johan Lugtenburg³

Affiliations

¹ Department of Chemistry, College of Applied and Industrial Science, University of Bahri, P.O. Box 11111, Khartoum 1660, Sudan. Stalab9@gmail.com.
² Department of Chemistry, College of Applied and Industrial Science, University of Bahri, P.O. Box 11111, Khartoum 1660, Sudan. kamaltha99@rediffmail.com.
³ Department of Chemistry, College of Applied and Industrial Science, University of Bahri, P.O. Box 11111, Khartoum 1660, Sudan. lugtenbu@chem.leidenuniv.nl.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carbon Radioisotopes / chemistry
Cyclization
Histidine / chemical synthesis*
Imidazoles / chemical synthesis
Isotope Labeling
Thiocyanates / chemistry*

Substances

Carbon Radioisotopes
Imidazoles
Thiocyanates
Histidine
thiocyanate