Phenyliodine(III) Bis(trifluoroacetate) Mediated Synthesis of 6-Piperidinylpurine Homo-N-nucleosides Modified with Isoxazolines or Isoxazoles^[1]

Abstract

The room temperature, 1,3-dipolar cycloaddition reactions of the nitrile oxide obtained from (6-piperidin-1-yl-9H-purin-9-yl)acetaldehyde oxime upon phenyliodine(III) bis(trifluoroacetate) treatment with excess unsaturated alcohols as solvent resulted in isoxazoline or isoxazole derivatives in almost quantitative yields. Analogous derivatives were prepared from the reactions of unsaturated phosphates. Preliminary biological tests indicated inhibition of lipid peroxidation for some of the examined compounds.

Key words

modified homo-N-nucleosides - isoxazolines - isoxazoles - 1,3-dipolar cycloaddition reactions - phenyliodine(III) bis(trifluoroacetate) - PIFA

• References

• 1 Preliminary communication presented at the 2nd Pharmaceutical Sciences Congress, October 9–11, 2014, Patra, Greece; Book of Abstracts, p 13 (EA017).
• 2a De Clercq E. J. Med. Chem. 2010; 53: 1438
• 2b Mehellou Y, De Clercq E. J. Med. Chem. 2010; 53: 621
• 2c De Clercq E. J. Med. Chem. 2005; 48: 1297
• 2d De Clercq E. Antiviral Res. 2007; 75: 1
• 2e Herdewijn P. Modified Nucleosides in Biochemistry, Biotechnology and Medicine. Wiley-VCH; Weinheim: 2008
• 2f Parker WB. Chem. Rev. 2009; 109: 2880
• 2g Mieczkowski A, Roy V, Agrofoglio LA. Chem. Rev. 2010; 110: 1828
• 2h Matsuda A, Sasaki T. Cancer Sci. 2004; 95: 105
• 3a Totowa NJ In Molecular and Cellular Basis of Inflammation . Serhan CN, Ward PA. Humana Press; New Jersey: 1999. Chap. 12, 259
• 3b Cronstein BN, Kramer SB, Weissmann G, Hirschhorn R. J. Exp. Med. 1983; 158: 1160
• 4 Crimmins MT. Tetrahedron 1998; 54: 9229
• 5 Blanco JM, Caamaño O, Fernández F, Rodríguez-Borges JE, Balzarini J, de Clercq E. Chem. Pharm. Bull. 2003; 51: 1060
• 6 Merino P. Curr. Med. Chem.: Anti-Infect. Agents 2002; 1: 389
• 7a Jager V, Colinas PA. Nitrile Oxides. In Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products. Padwa A, Pearson WH. John Wiley & Sons; New Jersey: 2003. Chap. 6, 361
• 7b Belen’kii LI. Nitrile Oxides. In Nitrile Oxides, Nitrones and Nitronates in Organic Synthesis, Novel Strategies in Synthesis. Feuer H. John Wiley & Sons; New Jersey: 2008
• 7c Kanemasa S. Heterocycles 2010; 82: 87
• 7d Chiacchio U, Padwa A, Romeo G. Curr. Org. Chem. 2009; 13: 422
• 7e Pan S, Amankulor NM, Zhao K. Tetrahedron 1998; 54: 6587
• 7f Xiang Y, Chen J, Schinazi RF, Zhao K. Bioorg. Med. Chem. Lett. 1996; 6: 1051
• 7g Li P, Gi H.-J, Sun L, Zhao K. J. Org. Chem. 1998; 63: 366
• 7h Gi H.-J, Xiang Y, Schinazi RF, Zhao K. J. Org. Chem. 1997; 62: 88
• 8a Herdewijn P. Biochim. Biophys. Acta 1999; 1489: 167
• 8b Chiacchio U, Genovese F, Iannazzo D, Librando V, Merino P, Rescifina A, Romeo R, Procopio A, Romeo G. Tetrahedron 2004; 60: 441
• 9 Balo C, Blanco JM, Fernandez F, Lens E, Lopez C. Tetrahedron 1998; 54: 2833
• 10a Thalassitis A, Hadjipavlou-Litina DJ, Litinas KE, Miltiadou P. Bioorg. Med. Chem. Lett. 2009; 19: 6433
• 10b Thalassitis A, Κatsori A.-M, Dimas K, Hadjipavlou-Litina DJ, Pyleris F, Sakellaridis N, Litinas KE. J. Enzyme Inhib. Med. Chem. 2014; 29: 109
• 11a Curran DP. J. Am. Chem. Soc. 1983; 105: 3826
• 11b Bode JW, Carreira EM. Org. Lett. 2001; 3: 1587
• 11c Maimone TJ, Shi J, Ashida S, Baran PS. J. Am. Chem. Soc. 2009; 131: 17066
• 11d Tabrizi MA, Baraldi BG, Guarneri M, Manfredini S, Pollini GP, Simoni D. Tetrahedron Lett. 1991; 32: 683
• 11e Muller J, Jager V. Tetrahedron Lett. 1982; 23: 4777
• 11f Tangallapally RP, Sun D, Rakesh, Budha N, Lee RE. B, Lenaerts AJ. M, Meibohm B, Lee RE. Bioorg. Med. Chem. Lett. 2007; 17: 6638
• 11g Zimmermann PJ, Blanarikova I, Jager V. Angew. Chem. Int. Ed. 2000; 39: 910
• 11h Kozikowski AP, Stein PD. J. Am. Chem. Soc. 1982; 104: 4023
• 12a Das B, Holla H, Mahender G, Banerjee J, Reddy MR. Tetrahedron Lett. 2004; 45: 7347
• 12b Concalves ES. B, Dos Santos M, Bernadat G, Bonnet-Delpon D, Crousse B. Beilstein J. Org. Chem. 2013; 9: 2387
• 12c Turner CD, Ciufolini MA. ARKIVOC 2011; (i): 410
• 12d Jawalekar AM, Reubsaet E, Rutjes FP. J. T, van Delft FL. Chem. Commun. 2011; 47: 3198
• 12e Chatterjee N, Pandit P, Halder S, Patra A, Maiti DK. J. Org. Chem. 2008; 73: 7775
• 12f Pinto A, Conti P, Grazioso G, Tamborini L, Madsen U, Nielsen B, De Micheli C. Eur. J. Med. Chem. 2011; 46: 787
• 12g Singh V, Hutait S, Biswas S, Batra S. Eur. J. Org. Chem. 2010; 531
• 12h Dirnens V, Skatsina I, Popelis J, Lukevics E. Chem. Heterocycl. Compd. 2007; 43: 193
• 12i Quadrelli P, Piccanello A, Mella M, Corsaro A, Pistara V. Tetrahedron 2008; 64: 3541
• 13a Mendelsohn BA, Lee S, Kim S, Teyssier F, Aulakh VS, Ciufolini MA. Org. Lett. 2009; 11: 1539
• 13b Yoshimura A, Zhu C, Middleton KR, Todora AD, Kastern BJ, Maskaev AV, Zhdankin VV. Chem. Commun. 2013; 49: 4800
• 13c Minakata S, Okumura S, Nagamachi T, Takeda Y. Org. Lett. 2011; 13: 2966
• 14a Kallitsakis MG, Yañez M, Soriano E, Marco-Contelles J, Hadjipavlou-Litina DJ, Litinas KE. Future Med. Chem. 2015; 7: 103
• 14b Thalassitis AN, Hadjipavlou-Litina DJ, Litinas KE. J. Heterocycl. Chem. 2015; 52: 366
• 14c Kallitsakis MG, Hadjipavlou-Litina DJ, Peperidou A, Litinas KE. Tetrahedron Lett. 2014; 55: 650
• 14d Kallitsakis MG, Hadjipavlou-Litina DJ, Litinas KE. J. Enzyme Inhib. Med. Chem. 2013; 28: 765
• 14e Thalassitis A, Litinas KE. Tetrahedron Lett. 2010; 51: 6451
• 15 Kozikowski AP, Ghosh AK. J. Org. Chem. 1984; 49: 2762
• 16 Ono N. The Nitro Group in Organic Synthesis . Wiley-VCH; Weinheim: 2001: 260
• 17a De Clercq E. Med. Res. Rev. 2013; 33: 1215
• 17b De Clercq E. Med. Res. Rev. 2013; 33: 1249
• 18a Stowell JK, Widlanski TS. Tetrahedron Lett. 1995; 36: 1825
• 18b Hojo M, Sakuragi R, Okabe S, Hosomi A. Chem. Commun. 2001; 357
• 18c Ye M.-C, Li L.-P, Zhao Y.-F, Zhai C. Phosphorus Sulfur Relat. Elem. 1988; 39: 79
• 18d Jung A, Engel R. J. Org. Chem. 1975; 40: 3652
• 18e Butsugan Y, Yamashita A, Araki S. J. Organomet. Chem. 1985; 287: 103
• 18f Delvos LB, Vyas DJ, Oestreich M. Angew. Chem. Int. Ed. 2013; 52: 4650