Iris L. Doerr

Nucleosides : XXX. Synthesis of 2-deoxy-2-fluoro-D-ribose

Abstract Crystalline 2-deoxy-2-fluoro- D -ribose (IVb) was prepared by debenzoylation of 1,3,4-tri-O-benzoyl-2-deoxy-2-fluoro-β- D -ribose (VIb). Reduction of 2′-deoxy-2′-fluorouridine (Ib) gave amorphous 1-(2-deoxy-2-fluoro-β- D -ribofuranosyl)-5,6-dihydrouracil (IIb), which was converted into crystalline 1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-β- D -ribosyl)-5,6-dihydrouracil (III). Glycosylic cleavage of IIb with dilute alkali, followed by heating with dilute acid, gave a mixture containing IVb. Benzoylation of impure IVb produced crystalline VIb. A second product, in amorphous form, probably 1,3,4-tri-O-benzoyl-2-deoxy-2-fluoro-α- D -ribose, was isolated; it also gave crystalline IVb upon debenzoylation. The pyranoid structure of VIb was proved as follows: replacement of the benzoyloxy group on C-1 by a methoxyl group gave methyl 3,4-di-O-benzoyl-2-deoxy-2-fluoro- D -riboside (VIII). Debenzoylation gave the unsubstituted glycoside IX, which was shown to be a pyranoside, thus establishing the ring structure of VIb. Methanolysis of IIb, followed by benzoylation, gave crystalline methyl 3,5-di-O-benzoyl-2-deoxy-2-fluoro- D -riboside (X) and amorphous VIII, as well as crystalline methyl 3-(N-benzoylureido)propionate (XII). Debenzoylation of X produced crystalline methyl 2-deoxy-2-fluoro- D -ribofuranoside (XI).