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http://dx.doi.org/10.13160/ricns.2015.8.1.48

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)
Publication Information
Journal of Integrative Natural Science / v.8, no.1, 2015 , pp. 48-55 More about this Journal
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
Anti-HIV Agents; 2'-Methyl-5'-deoxyphosphonic Acid Analogue; Vorbr${\ddot{u}}$ggen Reaction;
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1 P. N. Kumar and P. Parel, "Lamivudine for the treatment of HIV", Expert Opin. Drug Metab. Toxicol., Vol, 6, pp. 105-114, 2010.   DOI   ScienceOn
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.   DOI
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.   DOI   ScienceOn
4 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.   DOI   ScienceOn
5 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.   DOI   ScienceOn
6 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.   DOI
7 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.   DOI   ScienceOn
8 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.   DOI   ScienceOn
9 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.
10 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.   DOI   ScienceOn
11 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.   DOI   ScienceOn
12 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.
13 H. Vorbruggen and C. Ruh-Pohlenz, "Handbook of nucleoside synthesis", John Wiley & Sons. Inc., New York, 2001.
14 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.   DOI
15 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.   DOI   ScienceOn