Design, synthesis, and antiviral evaluation of some 3'-carboxymethyl-3'-deoxyadenosine derivatives.
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 H(2)/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.
Peterson
Matt A
MA
Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602, USA. matt_peterson@byu.edu
Ke
Pucheng
P
Shi
Houguang
H
Jones
Carl
C
McDougall
Brenda R
BR
Robinson
W Edward
WE
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002461:Cell Line, Transformed; D003839:Deoxyadenosines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D006678:HIV / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D019427:HIV Integrase / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure
D019380:Anti-HIV Agents; D003839:Deoxyadenosines; D019427:HIV Integrase