Synthesis of 5-(1-azidovinyl) and 5-[2-(1-azirinyl)] analogs of 2'-deoxyuridine

Article abstract of DOI:10.1139/v96-178

The regiospecific addition of bromine azide to the vinyl substituent of 5-vinyl-3',5'-di-O-acetyl- (or tert-butyldimethylsilyl)-2'-deoxyuridines (2) yielded the corresponding 5-(1-azido-2-bromoethyl)-3',5'-di-O-protected-2'-deoxyuridines (3). Treatment of the 5-(1-azido-2-bromoethyl) compounds 3 with t-BuOK, to effect the base-catalyzed elimination of HBr, afforded the corresponding 5-(1-azidovinyl)-2'-deoxyuridines (4,7). Thermal decomposition of 5-(1-azidovinyl)-2'-deoxyuridine (7) at 110°C in dioxane yielded 5-[2-(1-azirinyl)]-2'-deoxyuridine (9). 5-(1-Azidovinyl)-2'-deoxyuridine (7) exhibited appreciable in vitro antiviral activities against herpes simples virus type 1 (HSV-1) and varicella zoster virus (VZV). Although 7 increased the length of survival of HSV-1 brain-infected mice, it did not decrease the mortality rate relative to placebo. 5-[2-(1-Azirinyl)]-2'-deoxyuridine (9) was an inactive aniviral agent. The regiospecific addition of bromine azide to the vinyl substituent of 5-vinyl-3′,5′-di-O-acetyl- (or tert-butyldimethylsilyl)-2′-deoxyuridines (2) yielded the corresponding 5-(1-azido-2-bromoethyl)-3′, 5′-di-O-protected-2′-deoxyuridines (3). Treatment of the 5-(1-azido-2-bromoethyl) compounds 3 with t-BuOK, to effect the base-catalyzed elimination of HBr, afforded the corresponding 5-(1-azidovinyl)-2′-deoxyuridines (4, 7). Thermal decomposition of 5-(1-azidovinyl)-2′-deoxyuridine (7) at 110°C in dioxane yielded 5-[2-(1-azirinyl)]-2′-deoxyuridine (9). 5-(1-Azidovinyl)-2′-deoxyuridine (7) exhibited appreciable in vitro antiviral activities against herpes simplex virus type 1 (HSV-1) and varizella zoster virus (VZV). Although 7 increased the length of survival of HSV-1 brain-infected mice, it did not decrease the mortality rate relative to placebo. 5-[2-(1-Azirinyl)]-2′-deoxyuridine (9) was an inactive antiviral agent.