Asymmetric synthesis and antiviral activities of L-carbocyclic 2 ',3 '-didehydro-2 ',3 '-dideoxy and 2 ',3 '-dideoxy nucleosides

Asymmetric syntheses of L-carbocyclic 2',3'-didehydro-2',3'-dideoxy- and 2' ,3'-dideoxypyrimidine and purine nucleoside analogues were accomplished, an d their anti-HIV and anti-HBV activities were evaluated. The key intermedia te, (1S,4R)-1-benzoyloxy-4-(tert-butoxymethyl)cyclopent-2-ene (7), was prep ared by benzoylation of the alcohol 2, selective deprotection of the isopro pylidene group of 3, followed by thermal elimination via cyclic ortho ester or deoxygenation sia cyclic thionocarbonate. The target compounds were als o synthesized by thermal elimination via cyclic ortho esters from protected nucleosides. It was found that L-carbocyclic 2',3'-didehydro-2',3'-dideoxy adenosine (34) exhibited potent anti-HBV activity (EC50 = 0.9 mu M) and mod erate anti-HIV activity (EC50 = 2.4 mu M) in vitro without cytotoxicity up to 100 mu M.