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Synthesis and Conformation of Novel 3'-Branched Threosyl-5'-Deoxyphosphonic Acid Nucleoside Analogues

  • Shen, Guang Huan (BK-21 Project Team, College of Pharmacy, Chosun University) ;
  • Kang, Lien (BK-21 Project Team, College of Pharmacy, Chosun University) ;
  • Kim, Eun-Ae (BK-21 Project Team, College of Pharmacy, Chosun University) ;
  • Lee, Won-Jae (BK-21 Project Team, College of Pharmacy, Chosun University) ;
  • Hong, Joon-Hee (BK-21 Project Team, College of Pharmacy, Chosun University)
  • Received : 2012.03.28
  • Accepted : 2012.05.07
  • Published : 2012.08.20

Abstract

The discovery that threosyl phosphonate nucleoside (PMDTA, $EC_{50}=2.53{\mu}M$) is a potent anti-HIV agent has led to the synthesis and biological evaluation of 5'-deoxy versions of threosyl phosphonate nucleosides. In the present study, (E)-3'-phosphonoalkenyl and 3'-phosphonoalkyl nucleoside analogues 13, 16, 20 and 23 were synthesized from acetol and tested for anti-HIV activity and cytotoxicity. The adenine analogue 16 was found to exhibit moderate in vitro anti-HIV-1 activity ($EC_{50}=22.2{\mu}M$).

Keywords

References

  1. Holy, A. Curr. Pharm. Des. 2003, 9, 2567.
  2. De Clercq, E.; Holy, A. Nat. Rev. Drug Discovery 2005, 4, 928. https://doi.org/10.1038/nrd1877
  3. Vina, D.; Wu, T.; Renders, M.; Laflamme, G.; Herdewijn, P. Tetrahedron 2007, 63, 2634. https://doi.org/10.1016/j.tet.2007.01.032
  4. Schoning, K.; Scholz, P.; Guntha, S.; Wu, X.; Krishnamurthy, R.; Eschenmoser, A. Science 2000, 5495, 1347.
  5. Kempeneers, V.; Vastmans, K.; Rozenski, J.; Herdewijn, P. Nucleic Acids Res. 2003, 31, 6221. https://doi.org/10.1093/nar/gkg833
  6. Chaput, J. C.; Szostak, J. W. J. Am. Chem. Soc. 2003, 125, 9274. https://doi.org/10.1021/ja035917n
  7. Kempeneers, V.; Froeyen, M.; Vastmans, K.; Herdewijn, P. Chem. Biodivers 2004, 1, 112. https://doi.org/10.1002/cbdv.200490002
  8. Secrist, J. A. 3rd; Riggs, R. M.; Comber, R. N.; Montgomery, J. A. Nucleosides, Nucleotides 1992, 11, 947. https://doi.org/10.1080/07328319208021749
  9. Montgomery, J. A.; Thomas, H. J.; Kisliuk, R. L.; Gaumont, Y. J. Med. Chem. 1979, 22, 109. https://doi.org/10.1021/jm00187a024
  10. Liu, J. L.; Kim, E. A.; Hong, J. H. Nucleosides, Nucleotides & Nucleic Acids 2012, 31, 411. https://doi.org/10.1080/15257770.2012.670349
  11. Wang, W.; Jin, H.; Fuselli, N.; Mansour, T. S. Bioorg. Med. Chem. Lett. 1997, 7, 2567. https://doi.org/10.1016/S0960-894X(97)10048-8
  12. Wu, T.; Froeyen, M.; Kempeneers, V.; Pannecouque, C.; Wang, J.; Busson, R.; De Clercq, E.; Herdewijn, P. J. Am. Chem. Soc. 2005, 127, 5056. https://doi.org/10.1021/ja043045z
  13. Koh, Y. H.; Shim, J. H.; Wu, J. Z.; Zhong, W.; Hong, Z.; Girardet, J. L. J. Med. Chem. 2005, 48, 2867. https://doi.org/10.1021/jm049029u
  14. Kim, C. U.; Luh, B. Y.; Misco, P. F.; Bronson, J. J.; Hitchcock, M. J.; Ghazzouli, I.; Martin, J. C. J. Med. Chem. 1990, 33, 1207. https://doi.org/10.1021/jm00166a019
  15. Hong, J. H. Arch. Pharm. Res. 2007, 30, 131. https://doi.org/10.1007/BF02977684
  16. Kumamoto, H.; Topalis, D.; Broggi, J.; Pradere, U.; Roy, V.; Berteina-Raboin, S.; Nolan, S. P.; Deville-Bonne, D.; Andrei, G.; Snoeck, R.; Garin, D.; Crance, J.-M.; Agrofoglio, L. A. Tetrahedron 2008, 64, 3517. https://doi.org/10.1016/j.tet.2008.01.140
  17. Montagu, A.; Pradere, U.; Roy, V.; Nolan, S. P.; Agrofoglio, L. A. Tetrahedron 2011, 67, 5317.
  18. Huang, Q.; Herdewijn, P. J. Org. Chem. 2011, 76, 3742. https://doi.org/10.1021/jo200033p
  19. Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953. https://doi.org/10.1021/ol990909q
  20. Hockova, D.; Holy, A.; Masojidkova, M.; Keough, D. T.; De Jersey, J.; Guddat, L. W. Bioorg. Med. Chem. 2009, 17, 6218. https://doi.org/10.1016/j.bmc.2009.07.044
  21. Robins, M. J.; Uznanski, B. Can. J. Chem. 1981, 59, 2608. https://doi.org/10.1139/v81-375
  22. Vorbruggen, H.; Ruh-Pohlenz, C. New York, Handbook of Nucleoside Synthesis; 2001.
  23. Montgomery, J.; Hewson, K. J. Med. Chem. 1969, 12, 498. https://doi.org/10.1021/jm00303a605
  24. Tong, G. L.; Ryan, K. J.; Lee, W. W.; Acton, E. M.; Goodman, L. J. Org. Chem. 1967, 32, 859. https://doi.org/10.1021/jo01278a095
  25. Holy, A.; Votruba, I.; Merta, A.; Cerny, J.; Vesely, J.; Vlach, J.; Sediva, K.; Rosenberg, I.; Otmar, M.; Hrebabecky, H.; Travniekb, M.; Vonkac, V.; Snoeck, R.; De Clercq, E. Antiviral Res. 1990, 13, 295. https://doi.org/10.1016/0166-3542(90)90014-X
  26. Pauwels, R.; Balzarini, J.; Baba, M.; Snoeck, R.; Schols, D.; Herdewijn, P.; Desmyter, J.; De Clercq, E. J. Virol. Methods 1988, 20, 309. https://doi.org/10.1016/0166-0934(88)90134-6

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