SYNTHESIS OF HYDROPYRIDYL-3-CARBONYL)-2'-FLUORO-2'-DEOXYURIDINE (IVFRU-CDS) FOR BRAIN TARGETED DELIVERY OF IVFRU, AN ANTIVIRAL NUCLEOSIDE

hyl-1,4-dihydropyridyl-3-carbonyl)-2'-deoxyuridine (11) was synthesize d for future evaluation as a lipophilic, brain-selective, pyrimidine p hosphorylase-resistant, antiviral agent for the treatment of Herpes si mplex encephalitis (HSE). Treatment of (E)-5-(2-iodovinyl)-2'-fluoro-2 '-deoxyuridine (6) with TBDMSCl in the presence of imidazole in DMF yi elded the protected 5'-O-t-butyldimethylsilyl derivative (7). Subseque nt reaction with nicotinoyl chloride hydrochloride in pyridine afforde d arbonyl)-5'-O-t-butyldimethylsilyl-2'-deoxyuridine (8). Deprotection of the silyl ether moiety of 8 with n-Bu4N + F- and quaternization of the resulting 3'-O-(3-pyridylcarbonyl) derivative 9 using iodomethane afforded the corresponding 1-methylpyridinium salt 10. The latter was reduced with sodium dithionite to yield hyl-1,4-dihydropyridyl-3-carb onyl)-2'-deoxyuridine (11).