Asymmetric Synthesis and Antiviral Activities of l-Carbocyclic 2‘,3‘-Didehydro-2‘,3‘-dideoxy and 2‘,3‘-Dideoxy Nucleosides
- 1 August 1999
- journal article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 42 (17) , 3390-3399
- https://doi.org/10.1021/jm9901327
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 (EC50 = 0.9 μM) and moderate anti-HIV activity (EC50 = 2.4 μM) in vitro without cytotoxicity up to 100 μM.Keywords
This publication has 15 references indexed in Scilit:
- 1592U89, a novel carbocyclic nucleoside analog with potent, selective anti-human immunodeficiency virus activityAntimicrobial Agents and Chemotherapy, 1997
- BMS-200475, a novel carbocyclic 2′-deoxyguanosine analog with potent and selective anti-hepatitis B virus activity in vitroBioorganic & Medicinal Chemistry Letters, 1997
- Anti-human immunodeficiency and anti-hepatitis B virus activities of β-l-2′,3′-dideoxy purine nucleosidesBioorganic & Medicinal Chemistry Letters, 1996
- The anti-hepatitis B virus activities, cytotoxicities, and anabolic profiles of the (-) and (+) enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosineAntimicrobial Agents and Chemotherapy, 1992
- The Mechanism of Inhibition of Hepatitis B Virus Replication by the Carbocyclic Analog of 2′–DeoxyguanosineHepatology, 1992
- Fluorocarbocyclic nucleosides: synthesis and antiviral activity of 2'- and 6'-fluorocarbocyclic 2'-deoxyguanosinesJournal of Medicinal Chemistry, 1991
- Synthesis and anti-HIV activity of carbocyclic 2',3'-didehydro-2',3'-dideoxy 2,6-disubstituted purine nucleosidesJournal of Medicinal Chemistry, 1990
- Synthesis of SQ-33,054, a novel cyclobutane nucleoside with potent antiviral activityTetrahedron Letters, 1989
- Carbocyclic nucleosidesMedicinal Research Reviews, 1986
- Synthesis and Central Dopaminergic Effects of N-(4,6-Dimethyl-2-pyridinyl)benzamidesJournal of Medicinal Chemistry, 1985