Design, Synthesis, and Antiviral Evaluation of Some 3′-Carboxymethyl-3′-Deoxyadenosine Derivatives

Abstract

3′-Carboxymethyl-3′-deoxyadenosine derivatives were prepared from 2′-O-TBDMS-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 H2/Pd-C followed by treatment with p-nitrophenyl N-methylcarbamate. N 6-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.