Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Jan 1;20(1):60-4.
doi: 10.1016/j.bmcl.2009.11.031. Epub 2009 Nov 13.

Synthesis and evaluation of 3'-azido-2',3'-dideoxypurine nucleosides as inhibitors of human immunodeficiency virus

Hong-Wang Zhang  1 , Steven J Coats, Lavanya Bondada, Franck Amblard, Mervi Detorio, Ghazia Asif, Emilie Fromentin, Sarah Solomon, Aleksandr Obikhod, Tony Whitaker, Nicolas Sluis-Cremer, John W Mellors, Raymond F Schinazi
Affiliations

Synthesis and evaluation of 3'-azido-2',3'-dideoxypurine nucleosides as inhibitors of human immunodeficiency virus

Hong-Wang Zhang et al. Bioorg Med Chem Lett. .

Abstract

Based on the promising drug resistance profile and potent anti-HIV activity of beta-d-3'-azido-2',3'-dideoxyguanosine, a series of purine modified nucleosides were synthesized by a chemical transglycosylation reaction and evaluated for their antiviral activity, cytotoxicity, and intracellular metabolism. Among the synthesized compounds, several show potent and selective anti-HIV activity in primary lymphocytes.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Some important 3′-azido nucleosides.
Scheme 1
Scheme 1
Reagents and conditions: (a) TMSCl, (i-BuCO)2O, pyridine, rt, 4 h, 75%; (b) Bz2O, DMF, Et3N, rt 2 h, 74%; (c) (i) Tf2O, DCM, pyridine, 0 °C, (ii) H2O, (iii) MeOH, NaHCO3; 32%; (d) (i) MsCl, DCM, DMAP, 0 °C, 40 min, (ii) NaN3, DMF, 120 °C, 2 h, 65%, two steps; (e) NaOCH3/MeOH, DCM 45 °C, 4 h, 82%.
Scheme 2
Scheme 2
Reagents and conditions: (a) TosCl or TPPSCl, Et3N, DMAP, DCM, rt, 18 h 99%; 80%; (b) (i) R1H, (ii) NaOMe/MeOH, DCM 45 °C, 18 h, 55–73%.
Scheme 3
Scheme 3
Reagents and condition: (a) (i) BSA, CH3CN, 78 °C, 30 min, then TMSOTf, 75 °C, 18 h, 43%, (ii) TBAF, THF, rt, 4 h; (b) (i) anomer separation on silica gel, 43%, (ii) NH3/CH3OH, 110 °C, 18 h, 71%.
Scheme 4
Scheme 4
Reagents and condition: (a) (i) TBSCl, imidazole, DMF, rt, overnight, 80%, (ii) DIAD, TPP, 80 °C, 30 min, 75%, (iii) LiN3, DMF, 100 °C, 24 h, 70%; (b) purine base, BSA, TMSOTf, CH3CN, 70 °C, 18 h, 34–61%; (c) (i) TBAF/acetic acid (v/v: 1:0.2), THF, rt, 4–6 h, (ii) anomer separation on silica gel, (iii) nucleophilic reagents in the case of 2- and/or 6-chloro purines in one to three steps in 20–95% yield.
See this image and copyright information in PMC

References

    1. Kaufmann GR, Cooper DA. Curr. Opin. Microbiol. 2000;3:508. - PubMed
    1. Lewis W. Antiviral Ther. 2005;10:M13. - PubMed
    2. Pillay D, Taylor S, Richman DD. Rev. Med. Virol. 2000;10:231. - PubMed
    3. Ruane PJ, DeJesus EJ. Acquir. Immun. Defic. Syndr. 2004;37:S21. - PubMed
    4. Palacios R, Santos J, Camino X, Arazo P, Perea RT, Echevarrfa S, Ribera E, de la Rosa RS, Guillen SM. Curr. Ther. Res. 2005;66:117. - PMC - PubMed

    1. For example see: Lee K, Choi Y, Gumina G, Zhou W, Schinazi RF, Chu CK. J. Med. Chem. 2002;45:1313.; Schinazi RF, Lloyd RM, Jr., Nguyen MH, Cannon DL, McMillan A, Ilksoy N, Chu CK, Liotta DC, Bazmi HZ, Mellors JW. Antimicrob. Agents Chemother. 1993;37:875.; Feng JY, Shi J, Schinazi RF, Anderson KS. FASEB J. 1999;13:1511.

    1. Mitsuya H, Weinhold KJ, Furman PA, St. Clair MH, Lehrman SN, Gallo RC, Barry DW, Broker S. Proc. Natl. Acad. Sci. U.S.A. 1985;82:7096. - PMC - PubMed
    1. Pathak T. Chem. Rev. 2002;102:1623. - PubMed

Publication types

MeSH terms