A process for the preparation of fludarabine phosphate from 2-fluoroadenine

摘要

The invention provides a process for the preparation of fludarabine phosphate from 2-fluoroadenine and 9- beta -D-arabinofuranosyl-uracil using Enterobacter aerogenes (EBA). <??>2-Fluoroadenine is reacted with 9- beta -D-arabinosyl-uracile in a water solution at pH = 7 in the presence of EBA cell paste, to yield fludarabine. Fludarabine is then treated with acetic anhydride and the resulting acetylderivative is crystallised and hydrolysed to fludarabine. Phosphorylation and crystallisation afford fludarabine phosphate.