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

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.

Key words

oxathiaphosphorylation - gemcitabine 5′-O-phosphate - gemcitabine 5′-O-phosphoramidate - gemcitabine 5′-O-triphosphate

• References and Notes

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