| Abstract: |
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 5-0-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 (la). The 5’-0-benzoylated nucleoside 9a was further converted into the 5-bromo and 5-iodo analogues (lb and lc) by halogenation and debenzoylation. 2',3’-0-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 la from 5a. These new nucleosides, closely related to AZT, however, did not exhibit any significant anti-HIV activity in tissue culture using H9 cells. © 1990, American Chemical Society. All rights reserved. |
