Synthesis of 2 '-methylene-substituted 5-azapyrimidine, 6-azapyrimidine, and 3-deazaguanine nucleoside analogues as potential antitumor/antiviral agents

2'-Deoxy-2'-methylene-6-azauridine (5) and 2'-deoxy-2'-methylene-6-azacytid ine (8) have been synthesized via a multi-step procedure from 6-azauridine. 2'-Deoxy-2'-methylene-5-azacytidine (14a) and 2'-deoxy-2'-methylene-3-deaz aguanosine (19a) and their corresponding a-anomers (14b and 19b) have been synthesized by the transglycosylation of 3',5'-O-(1,1,3,3-tetraisopropyldis iloxan-1,3-diyl)-2'-deoxy-2'-methyleneuridine (12) with silylated 5-azacyto sine and silylated N-2-palmitoyl-3-deazaguanine, respectively, in the prese nce of trimethylsilyl trifluoromethanesulfonate as the catalyst in anhydrou s dichloroethane, followed by separation of the isomers and deprotection of the blocking groups. These compounds were tested for cytotoxicity against B16F10, L1210, and CCRF-CEM tumor cell lines and for antiviral activity aga inst HIV-1, HSV-1, and HSV-2.