Synthesis of 4-methylthio analogues of FLT and AZT and their evaluation against HIV.
Silylated 4-methylthiouracil and 4-methylthiothymine were condensed in the presence of TMS triflate with methyl 2,3-dideoxy-3-fluoro-5-O-(4- phenylbenzoyl)-D-erythro-pentofuranoside (3) and methyl 3-azido-5-O- (tert-butyldiphenylsilyl)-2,3-dideoxy-D-erythro-pentofuroside++ + (8), respectively, to give the corresponding nucleosides which were deprotected. The 3'-azido nucleoside was reduced with triphenylphosphine to the corresponding 3'-amino nucleoside. The 3'-amino nucleoside was also obtained by condensation of 4-methylthiothymidine with a 3-phthalimido sugar 14 followed by deprotection. The 4-methylthio analogue 11 of AZT showed moderate activity against HIV.
Abel-Rahman
A A
AA
Department of Chemistry, Odense University, Denmark.
Abdel-Bary
H M
HM
Pedersen
E B
EB
Nielsen
C
C
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D015215:Zidovudine; C002854:alovudine