Microwave-Assisted Click Chemistry for Nucleoside Functionalization: Useful Derivatives for Analytical and Biological Applications

Abstract

A series of novel 5-(1,2,3-triazolyl)-2′-deoxyuridines were synthesized using a simple and convenient one-step synthetic procedure via the Huisgen reaction. The key step in these syntheses is a click reaction at the C-5 position under solvent free microwave irradiation and CuI as a catalyst. 5-Azidomethyl-2′-deoxyuridine was synthesized from thymidine and its click reactions with several alkynes provided triazole derivatives in good yields. The synthesized compounds showed only marginal antiviral activities [against human rhinovirus (HRV), hepatitis C virus (HCV) and HIV] and antibacterial activities against a series of Gram positive and Gram negative bacteria. Evaluation of fluorescence properties of pyrene-modified and EPR studies of nitroxyl spin-labeled deoxyuridines demonstrate the applicability of these compounds as valuable analytical tools.

Key words

5-azidomethyl-2′-deoxyuridine - microwave irradiation - click chemistry - EPR - antibacterial

• References

• 1a De Clercq E. Curr. Opin. Virol. 2012; 2: 572
• 1b De Clercq E. Biochem. Pharmacol. 2011; 8: 299
• 2 Hatse S, De Clercq E, Balzarini J. Biochem. Pharmacol. 1999; 58: 539
• 3 Harris DG, Shao JY, Morrow BD, Zimmerman SS. Nucleosides, Nucleotides Nucleic Acids 2004; 23: 555
• 4 Blewett S, McGuigan C, Barucki H, Andrei G, Snoeck R, De Clercq E, Balzarini J. Nucleosides, Nucleotides Nucleic Acids 2001; 20: 1063
• 5a Patil VD, Wise DS, Wotring LL, Bloomer LC, Townsend LB. J. Med. Chem. 1985; 28: 423
• 5b Kifli N, De Clercq E, Balzarini J, Simons C. Bioorg. Med. Chem. 2004; 12: 4245
• 5c Amblard F, Aucagne V, Guenot P, Schinazi RF, Agrofoglio LA. Bioorg. Med. Chem. 2005; 13: 1239
• 5d McGuigan C, Brancale A, Barucki H, Srinivasan S, Jones G, Pathirana R, Carangio A, Blewett S, Luoni G, Bidet O, Jukes A, Jarvis C, Andrei G, Snoeck R, De Clercq E, Balzarini J. Antivir. Chem. Chemother. 2001; 12: 77
• 6a Skorobogatyi MV, Pchelintseva AA, Petrunina AL, Stepanova IA, Andronova VL, Galegov GA, Malakhov AD, Korshun VA. Tetrahedron 2006; 62: 1279
• 6b Nakatani K, Yoshida T, Saito I. J. Am. Chem. Soc. 2002; 124: 2118
• 7 Ciurea A, Fossey C, Benzaria S, Gavriliu D, Delbederi Z, Lelong B, Laduree D, Aubertin AM, Kirn A. Nucleosides Nucleotides 2001; 20: 1655
• 8 Amann N, Wagenknecht HA. Synlett 2002; 687
• 9 Gutierrez AJ, Terhorst TJ, Matteucci MD, Froehler BC. J. Am. Chem. Soc. 1994; 116: 5540
• 10 Winter HD, Herdewijn P. J. Med. Chem. 1996; 39: 4727
• 11a Seela F, Pujari SS, Schafer AH. Tetrahedron 2011; 67: 7418
• 11b Seela F, Xiong H, Budow S. Tetrahedron 2010; 66: 3930
• 12 Agrofoglio LA. Curr. Org. Chem. 2006; 10: 333
• 13 Lee YS, Park SM, Kim HM, Park SK, Lee K, Lee CW, Kim BH. Bioorg. Med. Chem. Lett. 2009; 19: 4688
• 14 Gramlich PM. E, Wirges CT, Gierlich J, Carell T. Org. Lett. 2008; 10: 249
• 15 Manfredini S, Vicentini CB, Manfrini M, Bianchi N, Rutigliano C, Mischiati C, Gambari R. Bioorg. Med. Chem. 2000; 8: 2343
• 16 Sidwell RW, Huffman JH, Khare GP, Allen LB, Witkowski JT, Robins RK. Science 1972; 177: 705
• 17 ElAkri K, Bougrin K, Balzarini BJ, Faraj A, Benhida R. Bioorg. Med. Chem. Lett. 2007; 17: 6656
• 18a Krim J, Sillahi B, Taourirte M, Rakib EM, Engels JW. ARKIVOC 2009; (xiii): 142
• 18b Krim J, Taourirte M, Engels JW. Molecules 2012; 17: 179
• 19a Moorhouse AD, Santos AM, Gunaratnam M, Moore M, Neidle S, Moses JE. J. Am. Chem. Soc. 2006; 128: 15972
• 19b Lee LV, Mitchell ML, Huang S.-J, Fokin VV, Sharpless KB, Wong C.-H. J. Am. Chem. Soc. 2003; 125: 9588
• 20a Wu P, Feldman AK, Nugent AK, Hawker CJ, Scheel A, Voit B, Pyun J, Frechet JM. J, Sharpless KB, Fokin VV. Angew. Chem. Int. Ed. 2004; 43: 3928
• 20b Wu P, Malkoch M, Hunt JN, Vestberg R, Kaltgrad E, Finn MG, Fokin VV, Sharpless KB, Hawker CJ. Chem. Commun. 2005; 5775
• 20c Rozkiewicz DI, Janczewski D, Verboom W, Ravoo BJ, Reinhoudt DN. Angew. Chem. Int. Ed. 2006; 45: 5292
• 21a Wang Q, Chan TR, Hilgraf R, Fokin VV, Sharpless KB, Finn MG. J. Am. Chem. Soc. 2003; 125: 3192
• 21b Speers AE, Adam GC, Cravatt BF. J. Am. Chem. Soc. 2003; 125: 4686
• 21c Speers AE, Cravatt BF. Chem. Biol. 2004; 11: 535
• 21d Burley GA, Gierlich J, Mofid MR, Nir H, Tal S, Eichen Y, Carell T. J. Am. Chem. Soc. 2006; 128: 1398
• 22 Chittepu P, Sirivolu VR, Seela F. Bioorg. Med. Chem. 2008; 16: 8427
• 23 Sablón-Carrazana M, Jiménez-Alemán G, Pérez Perera R, Vélez-Castro H, Rodríguez Tanty C. Rev. CEN CienQuím. 2007; 38: 237
• 24 Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that grow Aerobically, Approved Standard M7-A7. 7th ed., Vol. 26 Clinical and Laboratory Standards Institute (CLSI); Wayne (PA, USA): 2006: Number 2
• 25 Pannecouque C, Daelemans D, De Clercq E. Nat. Protoc. 2008; 3: 427
• 26a Malinovskii VL, Wenger D, Haener R. Chem. Soc. Rev. 2010; 39: 410
• 26b Sinkeldam RW, Greco N, Tor Y. Chem. Rev. 2010; 110: 2579
• 26c Balakin KV, Korshun VA, Mikhalev II, Maleev GV, Malakhov AD, Prokhorenko IA, Berlin Yu A. Biosens. Bioelectron. 1998; 13: 771
• 27a Wojczewski C, Stolze K, Engels JW. Synlett 1999; 1667
• 27b Hawkins ME. Cell. Biochem. Biophys. 2001; 34: 257
• 28 Krim J, Gruenewald C, Taourirte M, Engels JW. Bioorg. Med. Chem. 2012; 20: 480
• 29 Demas JN, Crosby GA. J. Phys. Chem. 1971; 75: 991
• 30a Krstić I, Endeward B, Margraf D, Marko A, Prisner T. Top. Curr. Chem. 2012; 321: 159
• 30b Bordignon E. Top. Curr. Chem. 2012; 321: 121
• 31 Shelke SA, Sigurdsson ST. Eur. J. Org. Chem. 2012; 12: 2291
• 32 Klug CS, Feix JB. Methods and Applications of Site-Directed Spin Labeling EPR Spectroscopy. In Biophysical Tools for Biologists: In Vitro Techniques. Elsevier Academic Press Inc; San Diego: 2008. Vol. 84. 617-658
• 33 Ding P, Wunnicke D, Steinhoff HJ, Seela F. Chem. Eur. J. 2010; 16: 14385
• 34 Stoll S, Schweiger A. J. Magn. Reson. 2006; 178: 42