SYNTHESIS OF 5-(1-ARIDOVINYL) AND 5-[2-(1-AZIRINYL)] ANALOGS OF 2'-DEOXYURIDINE

The regiospecific addition of bromine azide to the vinyl substituent o f 5-vinyl-3',5'-di-O-acetyl- (or tert-butyldimethylsilyl)-2'-deoxyurid ines (2) yielded the corresponding -bromoethyl)-3',5'-di-O-protected-2 '-deoxyuridines (3). Treatment of the 5-(1-azido-2-bromoethyl) compoun ds 3 with t-BuOK, to effect the base-catalyzed elimination of HBr, aff orded the corresponding 5-(1-azidovinyl)-2'-deoxyuridines (4, 7). Ther mal decomposition of 5-(1-azidovinyl)-2'-deoxyuridine (7) at 110 degre es C in dioxane yielded 5-[2-(1-azirinyl)]-2'-deoxyuridine (9). 5-(1-A zidovinyl)-2'-deoxyuridine (7) exhibited appreciable in vitro antivira l activities against herpes simplex virus type 1 (HSV-1) and varizella tester virus (VZV). Although 7 increased the length of survival of HS V-1 brain-infected mice, it did not decrease the mortality rate relati ve to placebo. 5-[2-(1-Azirinyl)]-2'-deoxyuridine (9) was an inactive antiviral agent.