SYNTHESIS OF VARIOUS 3'-BRANCHED 2',3'-UNSATURATED PYRIMIDINE NUCLEOSIDES AS POTENTIAL ANTI-HIV AGENTS

A series of four new 2',3'-dideoxypyrimidine nucleosides was synthesized and their activity against HIV was evaluated. Coupling of a suitably protected 3-methylidene xylofuranose derivative 5 with thymine and uracil afforded branched nucleosides 7a and 7b. The latter was transformed into 2',3'-dideoxy-2',3'-didehydro 3'-branched nucleoside 1 by Barton deoxygenation during which an allylic rearrangement occurred. Compounds 7a and 7b were converted into the corresponding 2,2'-anhydro derivatives by an intramolecular Mitsunobu reaction. Treatment of these compounds with LiN3 in DMF afforded the branched azidonucleosides by S(N)2' reaction. Palladium-catalyzed azidation of the allylic ester 6a allowed the introduction of an azido group in a highly regio- and stereoselective manner at C-2', affording 12. The p-anisyl group employed for the protection of the primary hydroxyl of 5 was stable in acidic and basic conditions, allowing its removal only at the end of the synthesis.