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
. 2008 Sep 15;16(18):8379-89.
doi: 10.1016/j.bmc.2008.08.041. Epub 2008 Aug 26.

Synthesis and antiviral evaluation of acyclic azanucleosides developed from sulfanilamide as a lead structure

Rafał Gawin  1 , Erik De Clercq, Lieve Naesens, Mariola Koszytkowska-Stawińska
Affiliations

Synthesis and antiviral evaluation of acyclic azanucleosides developed from sulfanilamide as a lead structure

Rafał Gawin et al. Bioorg Med Chem. .

Abstract

The acyclic azanucleosides with 2-, 3-, or 4-aminobenzenesulfonyl function at the nitrogen atom of the sugar mimic were prepared by coupling of 2-, 3-, or 4-nitro-N-(2-pivaloyloxyethyl)-N-(pivaloyloxymethyl)benzenesulfonamide with the silylated pyrimidine nucleobases followed by the reduction of the nitro group with sodium dithionite in aqueous solution or the palladium-catalysed transfer hydrogenation. The azanucleosides were evaluated for, but found to be devoid of, activity against several RNA- and DNA-viruses in vitro.

PubMed Disclaimer

Figures

None
Graphical abstract
Figure 1
Figure 1
Nucleoside analogs containing 2-, 3-, or 4-aminobenzenesulfonyl function.
Scheme 1
Scheme 1
Reagents and conditions: (i) pyridine, dichloromethane, room temperature, overnight; (ii) PivOCH2Cl, K2CO3, DMF, room temperature, 5 days; (iii) a—nucleobase, BSA, acetonitrile, room temperature, 1 h; b—TMSOTf, acetonitrile, room temperature, 2 days. (iv) a—5-fluorouracil, BSA, acetonitrile, room temperature, 1 h; b—SnCl4, acetonitrile, dichloromethane, room temperature, 2 days.
Figure 2
Figure 2
1H–13C HMBC correlations observed for 5a, and 1H–1H ROESY correlations for 5b and 5d.
Scheme 2
Scheme 2
Reagents and conditions: (i) Na2S2O4, 4% NaOH aq, 90 °C, 1 h; (ii) Na2S2O4 aq, 90 °C, 1 h; (iii) NH3 aq, MeOH, 70 °C, 1 day.
Scheme 3
Scheme 3
Reagents and conditions: (i) cyclohexene, 10% Pd/C, EtOH, 60 °C, 1 day.
Scheme 4
Scheme 4
Reagents and conditions: cyclohexene, 10% Pd/C, 60 °C, 1 day: (i) EtOH; 11a:10a = 3:2 (1H NMR); (ii) MeOH; (iii) 1,4-dioxane.
Scheme 5
Scheme 5
Reagents and conditions: (i) NH3 aq, MeOH, 70 °C, 1 day; (ii) NaOH aq (4%), 90 °C, 2 h.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. De Clercq E. J. Clin. Virol. 2004;30:115. - PubMed
    2. Galmarini C.M., Mackey J.R., Dumontet C. Lancet Oncol. 2002;3:415. - PubMed
    3. Opio C.K., Lee W.M., Kirkpatrick P. Nat. Rev. Drug Disc. 2005;4:535. - PubMed
    1. Johnson A.A., Ray A.S., Hanes J., Suo Z., Colacino J.M., Anderson K.S., Johnson K.A. J. Biol. Chem. 2001;276:40847. - PubMed
    2. De Clercq E. J. Antimicrob. Chemother. 2003;51:1079. - PubMed
    3. Jeha S., Gandhi V., Chan K.W., McDonald L., Ramirez I., Madden R., Rytting M., Brandt M., Keating M., Plunkett W., Kantarjian H. Blood. 2004;103:784. - PubMed
    1. Gumina G., Olgen S., Chu C.K. In: Antiviral Nucleosides: Chiral Synthesis and Chemotherapy. Chu C.K., editor. Elsevier B.V.; 2003. pp. 161–169.
    1. Markham A.F., Newton C.R., Porter R.A., Sim I.S. Antiviral Res. 1982;2:319. For 5′-deoxy-5′-sulfonamidofuranosyl nucleosides, see: - PubMed
    2. Cosstick R., Jones A.S., Walker R.T. Tetrahedron. 1984;40:427.
    3. Elliott R.D., Brockman R.W., Montgomery J.A. J. Med. Chem. 1986;29:1052. - PubMed
    4. Sim I.S., Picton C., Cosstick R., Jones A.S., Walker R.T., Chamiec A.J. Nucleosides Nucleotides. 1988;7:129.
    5. Martin J.A., Duncan I.B., Hall M.J., Wong-Kai-In P., Lambert R.W., Thomas G.J. Nucleosides Nucleotides. 1989;8:753.
    6. Homma H., Watanabe Y., Abiru T., Murayama T., Nomura Y., Matsuda A. J. Med. Chem. 1992;35:2881. - PubMed
    7. Criton M., Dewyntert G., Aouf N., Montero J.-L., Imbach J.-L. Nucleosides Nucleotides. 1995;14:1795.
    8. Sharma M., Li Y.X., Ledvina M., Bobek M. Nucleosides Nucleotides. 1995;14:1831.
    9. Urjasz W., Celewicz L., Golankiewicz K. Nucleosides Nucleotides. 1996;15:1189.
    10. Martin J.A., Thomas G.J., Merret J.H., Lambert R.W., Bushnel D.J., Dundson S.J., Freeman A.C., Hopkins R.A., Johns I.R., Keech E., Simmonite H., Wong-Kai-In P., Holland M. Antiviral Chem. Chemother. 1998;1:1. - PubMed
    11. Scherman M.S., Winans K.A., Stern R.J., Jones V., Bertozzi C.R., McNeil M.R. Antimicrob. Agents Chemother. 2003;47:378. - PMC - PubMed
    12. Vanada J., Bennet E., Wilson D., Bishoff H., Barry C., Aldrich C. Org. Lett. 2006;8:4707. - PMC - PubMed
    1. Van Calenbergh S., Van Den Eeckhout E., Herdewijn P., De Bruyn A., Verlinde C., Hol W., Callens M., Van Aerschot A., Rozenski J. Helv. Chim. Acta. 1994;77:631. For 3′-deoxy-3′-sulfonamidofuranosyl nucleosides, see:
    2. Yamana K., Ohashi Y., Nunota K., Nakano H. Tetrahedron. 1997;53:4265.

Publication types

LinkOut - more resources