Design, synthesis, and antiviral evaluation of some 3′-carboxymethyl-3′-deoxyadenosine derivatives

3'-Carboxymethyl-3'-deoxyadenosine derivatives were prepared from 2'-O-TBDMS3 3'-[(ethoxycarbonyl) methyl]-3'-deoxyadenosine (1) via simple and efficient procedures. Conversion of 1 to its 5'-azido-5'-deoxy derivative 5 was accomplished via a novel one-pot method employing 5'-activation (TosCl) followed by efficient nucleophilic displacement with tetramethylguanidinium azide. Compound 5 was converted to 5'-[(N-methylcarbamoyl)amino] derivative 8 via one-pot reduction/acylation employing H-2/Pd-C followed by treatment with p-nitrophenyl N-methylcarbamate. N6-phenylcarbamoyl groups were introduced by treatment with phenylisocyanate, and an efficient new method for lactonization of 2'-O-TBDMS-3'-[(ethoxycarbonyl) methyl]-3'-deoxyadenosines to give corresponding 2', 3'-lactones was also developed. Target compounds were evaluated for anti-HIV and anti-HIV integrase activities, but were not active at the concentrations tested.