Tuesday, June 19, 2007 - 1:55 PM
The Merlins (Boise Centre on the Grove)

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

Matt A. Peterson, Houguang Shi, and Pucheng Ke. Brigham Young University, Provo, UT

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 5'-azido-2'-O-TBDMS-5'-deoxy-3'-[(ethoxycarbonyl)methyl]-3'-deoxyadenosine (2) was accomplished via a novel one-pot method employing 5'-activation (TosCl) followed by efficient nucleophilic displacement with tetramethylguanidinium azide. Compound 2 was converted to a 5'-[(N-methylcarbamoyl)amino] derivative (3) via one-pot reduction/acylation employing H2/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.