Synlett 2014; 25(13): 1851-1854
DOI: 10.1055/s-0034-1378353
letter
© Georg Thieme Verlag Stuttgart · New York

Efficient Synthesis of Gemcitabine 5′-O-Triphosphate Using Gemcitabine 5′-O-Phosphoramidate as an Intermediate

Renata Kaczmarek
a  Department of Bioorganic Chemistry, Center of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland   Fax: +48(42)6815483   Email: baraniak@cbmm.lodz.pl
,
Ewa Radzikowska
a  Department of Bioorganic Chemistry, Center of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland   Fax: +48(42)6815483   Email: baraniak@cbmm.lodz.pl
,
Janina Baraniak*
a  Department of Bioorganic Chemistry, Center of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland   Fax: +48(42)6815483   Email: baraniak@cbmm.lodz.pl
b  Institute of Chemistry, Environmental Protection and Biotechnology, Jan Długosz University, Armii Krajowej 13/15, 42-201 Częstochowa, Poland
› Author Affiliations
Further Information

Publication History

Received: 15 April 2014

Accepted after revision: 28 May 2014

Publication Date:
09 July 2014 (online)


Abstract

A new efficient approach for the synthesis of gemcitabine triphosphate has been developed. The method is based on the ring-opening reaction of 2-cyanoethoxy-2-oxo-1,3,2-oxathia­phospholane with protected gemcitabine in the presence of DBU. Subsequent treatment of gemcitabine monophosphate with DCC in the presence of ammonia provides gemcitabine 5′-O-phosphoramidate. Finally, this compound, on reaction with pyrophosphate, furnishes gemcitabine 5′-triphosphate in 50% yield.

Supporting Information

 
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