Journal of Integrative Natural Science (통합자연과학논문집)

The Basic Science Institute Chosun University (조선대학교 기초과학연구원)
권호 표지
DOI QR코드

DOI QR Code

Synthesis of Novel 2'(β)-Methyl-5'-deoxyapiose Nucleoside Phosphonic Acid Analogues as Antiviral Agents

  • Hong, Joon Hee (BK-21 Project Team, College of Pharmacy, Chosun University)
  • Received : 2015.03.01
  • Accepted : 2015.03.25
  • Published : 2015.03.30
Download PDF
⟨ Previous Next ⟩

Abstract

Novel 2'(${\beta}$)-methyl-5'-deoxyapiose purine phosphonic acid analogues were designed and synthesized from 2-propanone-1,3-diacetate. Condensation successfully proceeded from a glycosyl donor 9 under Vorbr${\ddot{u}}$ggen conditions. Condensation of aldehyde 14 with Wittig reagent [(diethoxyphosphinyl)methylidene] triphenylphosphorane gave the desired nucleoside phosphonate analogues 15. Ammonolysis and hydrolysis of phosphonates gave the nucleoside phosphonic acid analogue 17 and 19. The synthesized nucleoside analogues were subjected to antiviral screening against HIV-1. The adenine analogue 19 exhibited weak in vitro activities against HIV-1.

Keywords

References

  1. P. N. Kumar and P. Parel, "Lamivudine for the treatment of HIV", Expert Opin. Drug Metab. Toxicol., Vol, 6, pp. 105-114, 2010. https://doi.org/10.1517/17425250903490418
  2. V. Nair and T. Tahnke, "Antiviral activities of isomeric dideoxynucleosides of D- and L-related stereochemistry", Antimicrob. Agents Chemother., Vol. 39, pp. 1017-1029, 1995. https://doi.org/10.1128/AAC.39.5.1017
  3. T. Wu, M. Froeyen, V. Kempeneers, C. Pannecouque, J. Wang, R. Busson, E. De Clercq, and P, Herdewijn, "Deoxythreosyl phosphonate nucleosides as selective anti-HIV agents", J. Am. Chem. Soc., Vol. 127, pp. 5056-5065, 2005. https://doi.org/10.1021/ja043045z
  4. K. Schoning, P. Scholz, S. Guntha, X, Wu, R. Krishnamurthy, and A. Eschenmoser, "Chemical etiology of nucleic acid structure: the alpha-threofuranosyl-(3'${\rightarrow}$2') oligonucleotide system", Science, Vol. 5495, pp. 1347-1351, 2000.
  5. V. Kempeneers, K. Vastmans, J. Rozenski, and P. Herdewijn, "Recognition of threosyl nucleotides by DNA and RNA polymerases", Nucleic Acids Res., Vol. 31, pp. 6221-6226, 2003. https://doi.org/10.1093/nar/gkg833
  6. V. Kempeneers, M. Froeyen, K. Vastmans, and P. Herdewijn, "Influence of threose nucleoside units on the catalytic activity of a hammerhead ribozyme", Chem. Biodivers., Vol. 1, pp. 112-123, 2004. https://doi.org/10.1002/cbdv.200490002
  7. D. Vina, T. Wu, M. Renders, G. Laflamme, and P. Herdewijn, "Synthesis of 3'-O-phosphonomethyl nucleosides with an adenine base moiety", Tetrahedron, Vol. 63, pp. 2634-2646, 2007. https://doi.org/10.1016/j.tet.2007.01.032
  8. D. A. Fort, T. J. Woltering, A. M. Alker, and T. Bach, "Photochemical reactions of prop-2-enyl and prop-2-ynyl substituted 4-aminomethyl- and 4-oxymethyl-2(5H)-furanones", Heterocycles, Vol. 88, pp. 1079-1100, 2004.
  9. H. Vorbruggen and C. Ruh-Pohlenz, "Handbook of nucleoside synthesis", John Wiley & Sons. Inc., New York, 2001.
  10. G. H. Jones and J. G. Moffatt, "The synthesis of 6'-deoxyhomonucleoside 6'-phosphonic acid", J. Am. Chem. Soc., Vol. 90, pp. 5337-5338, 1968. https://doi.org/10.1021/ja01021a086
  11. Y. Xu, M. T. Flavin, and Z. Q. Xu, "Preparation of new Wittig reagents and their application to the synthesis of ${\alpha},{\beta}$-unsaturated phosphonates", J. Org. Chem., Vol. 61, pp. 7697-7701, 1996. https://doi.org/10.1021/jo9608275
  12. D. Hockova, A. Holy, M. Masojidkova, D. T. Keough, J. De Jersey, and L. W. Guddat, "Synthesis of branched 9-[2-(2-phosphonoethoxy)ethyl]purines as a new class of acyclic nucleoside phosphonates which inhibit Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase", Bioorg. Med. Chem., Vol. 17, pp. 6218-6232, 2009. https://doi.org/10.1016/j.bmc.2009.07.044
  13. Q. Huang and P.Herdewijn, "Synthesis of (E)-3'-phosphonoalkenyl modified nucleoside phosphonates via a highly stereoselective olefin cross-metathesis reaction", J. Org. Chem., Vol. 76, pp. 3742-3753, 2011. https://doi.org/10.1021/jo200033p
  14. Y. Koyanagi. S. Harada, M. Takahashi, F. Uchino, and N.Yamamoto, "Selective cytotoxicity of AIDS virus towards HTLV-1 transformed cell lines", Int. J. Cancer, Vol. 36, pp. 445-451, 1985. https://doi.org/10.1002/ijc.2910360406
  15. R. Pauwels, J. Balzarini, M. Baba, R. Snoeck, D. Schols, P. Herdewijn, J. Desmyter, and E. De Clercq, "Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds", J. Virol. Methods, Vol. 20, pp. 309-321, 1988. https://doi.org/10.1016/0166-0934(88)90134-6