2'-azido-2',3'-dideoxypyrimidine nucleosides. Synthesis and antiviral activity against human immunodeficiency virus.
A series of four 2'-azido-2',3'-dideoxypyrimidine nucleosides were synthesized and their activity against human immunodeficiency virus was explored. 2,2'-Anhydro-5-O-benzoyluridine (6a) was prepared from 5-O-benzoyluridine (5a) and converted into 3'-deoxy analogue 8a by imidazolylthiocarbonylation followed by Bu3SnH reduction. Treatment of 8a with LiN3 in DMF followed by saponification afforded 2'-azido-2',3'-dideoxyuridine (1a). The 5'-O-benzoylated nucleoside 9a was further converted into the 5-bromo and 5-iodo analogues (1b and 1c) by halogenation and debenzoylation. 2',3'-O-Isopropylideneuridine (3) was converted in two steps into the thymine nucleoside, which was benzoylated and de-O-isopropylidenated to afford 5'-O-benzoyl-5-methyluridine (5d). 2'-Azido-2',3'-dideoxy-5-methyluridine (1d) was synthesized from 5d in a similar manner as that used for the synthesis of 1a from 5a. These new nucleosides, closely related to AZT, however, did not exhibit any significant anti-HIV activity in tissue culture using H9 cells.
Warshaw
J A
JA
Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Division of Graduate School of Medical Sciences, Cornell University, New York, New York 10021.
Watanabe
K A
KA
D000998:Antiviral Agents / Q000138:chemical synthesis*; D006678:HIV / Q000187:drug effects*; D006801:Humans; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D000998:Antiviral Agents; D015215:Zidovudine