SYNTHESIS OF 1'-[C-14]-STAVUDINE(R) (D4T)

Dideoxy-beta-D-glyceropent-2'-enofuranosyl)thymine (1'-[C-14]-d4T), wa s synthesized from 1-[C-14]-ribose, 1,in 7 steps in an overall yield o f 29.3%. 1-[C-14]-Ribose was converted in one step to 1-O-methyl-2,3,5 -tri-O-benzoylribofuranoside 2 in quantitative yield. Compound 2 was c onverted to its beta-1-O-acetyltribenzoyl derivative, 3 which was coup led with thymine and subsequently deprotected to give 1'-[C-14]-5-meth yluridine, 5 in 56.0% yield from 1. Compound 5 was converted to its 2' ,3',5'-tri-O-methanesulfonate derivative, 6 in quantitative yield. In a ''one-pot'' transformation involving three consecutive transformatio ns, compound 6 was converted to 1'-[C-14]-5'-benzoyl-d4T, 10 in 94.5% yield. Methanolysis of 10 followed by flash chromatography gave the ti tle compound in 79.0% yield (99.9% radiochemical purity, and 98.6% pot ency as determined by HPLC weight assay).