Stereospezifische Synthese des Cancerostatikums 5′‐Desoxy‐5‐fluor‐uridin (5‐DFUR) und seiner 5′ ‐deuterierten Derivate

Abstract

Stereospecific Synthesis of the Anticancer Agent 5′‐Deoxy‐5‐fluorouridine and its 5′‐deuteriated Derivatives 5′‐Deoxy‐5‐fluorouridine (5′‐DFUR) has been obtained in high yield and purity by Stereospecific condensation of the anomeric 5¨deoxy‐1,2,3‐tri‐ O ‐acetyl‐D‐ribofu‐ranose with bis(trimethylsilylated)‐5‐fluorouracil in the presence of trimethylsilyl trifluoromethanesulfonate, and by subsequent cleavage of the acetate protecting groups. A minor by‐product of the synthesis, the α‐anomeric nucleoside is produced by a (β‐α)‐epimerization, a procedure which is catalyzed by trimethylsilyl trifluoromethanesulfonate. The corresponding 5′‐deuteriated, and 5′,5′‐dideuteriated nucleosides have also been synthesized using an analogous way. The synthesis of the sugar components of the latter nucleosides ‐ starting from D‐ribose, D‐xylose and D‐glucose ‐is also described.