Document Report Card

ID: ALA1132363

Journal: J Med Chem

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

Authors: Wang P, Gullen B, Newton MG, Cheng YC, Schinazi RF, Chu CK.

Abstract: Asymmetric syntheses of L-carbocyclic 2',3'-didehydro-2',3'-dideoxy- and 2',3'-dideoxypyrimidine and purine nucleoside analogues were accomplished, and their anti-HIV and anti-HBV activities were evaluated. The key intermediate, (1S, 4R)-1-benzoyloxy-4-(tert-butoxymethyl)cyclopent-2-ene (7), was prepared by benzoylation of the alcohol 2, selective deprotection of the isopropylidene group of 3, followed by thermal elimination via cyclic ortho ester or deoxygenation via cyclic thionocarbonate. The target compounds were also synthesized by thermal elimination via cyclic ortho esters from protected nucleosides. It was found that L-carbocyclic 2',3'-didehydro-2',3'-dideoxyadenosine (34) exhibited potent anti-HBV activity (EC(50) = 0.9 microM) and moderate anti-HIV activity (EC(50) = 2.4 microM) in vitro without cytotoxicity up to 100 microM.

CiteXplore: 10464025

DOI: 10.1021/jm9901327