3'-Carboxymethyl-3'-deoxyadenosine derivatives were prepared from 2'-O-TBDMS-3'-deoxy-3'-[(ethoxycarbonyl)methyl]adenosine (1) via simple and efficient procedures. Conversion of 1 to 5'-azido-2'-O-TBDMS-3', 5'-dideoxy -3'-[(ethoxycarbonyl) methyl] adenosine (4) was accomplished via a novel one-pot method employing 5'-activation (TosCl) followed by efficient nucleophilic displacement with tetramethylguanidinium azide. Compound 4 was converted to a 5'-[(N-methylcarbamoyl)amino] derivative (5) via one-pot reduction/acylation employing H2/Pd-C followed by treatment with p-nitrophenyl N-methylcarbamate. The latter step of this two-step process required an efficient source of p-nitrophenyl N-methylcarbamate, thus a highly efficient new method for preparing p-nitrophenyl N-alkylcarbamate was developed. N6-phenylcarbamoyl groups were introduced by treatment with phenylisocyanate, and an efficient new method for lactonization of 2'-O-TBDMS-3'-deoxy-3'-[(ethoxycarbonyl)methyl]adenosines 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.
College and Department
Physical and Mathematical Sciences; Chemistry and Biochemistry
BYU ScholarsArchive Citation
Shi, Houguang, "Synthesis and Antiviral Evaluation of Some 3'-Carboxymethyl-3'-deoxyadenosine Derivatives" (2007). Theses and Dissertations. 1010.
3'-Carboxymethyl-3'-deoxyadenosine, nucleoside, carbamate