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Journal of Flow Chemistry

, Volume 5, Issue 4, pp 216–219 | Cite as

Studies on the Continuous-Flow Synthesis of Nonpeptidal bis-Tetrahydrofuran Moiety of Darunavir

  • Raquel A. C. Leão
  • Raquel O. de Lopes
  • Marco A. de M. Bezerra
  • Mauro N. Muniz
  • Bruna B. Casanova
  • Simone C. B. Gnoatto
  • Grace Gosmann
  • Laszlo Kocsis
  • Rodrigo O. M. A. de Souza
  • Leandro S. M. de Miranda
Full Paper

Abstract

The use of continuous-flow chemistry has shown to be an important tool in improving API manufacture. In the present paper, we report the use of continuous-flow reactors in the synthesis of the bicyclic side chain of antiretroviral Darunavir.

Keywords

bis-tetrahydrofuran HIV protease continuous flow 

Supplementary material

41981_2015_5040216_MOESM1_ESM.pdf (452 kb)
Supplementary material, approximately 463 KB.

References

  1. 1.(a)
    Microreactors; Ehrfeld, W.; Hessel, V.; Löwe, H., Eds.; Wiley-VCH: Weinheim, 2000CrossRefGoogle Scholar
  2. 2.(b)
    Chemical MicroProcess Engineering; Hessel, V.; Hardt, S.; Löwe, H., Eds.; Wiley-VCH: Weinheim, 2004Google Scholar
  3. 2.(c)
    Microreactors in Organic Synthesis; Wirth, T., Ed., Wiley-VCH: Weinheim, 2008Google Scholar
  4. 2.(d)
    Flash Chemistry: Fast Organic Synthesis in Microsystems, Yoshida, J., Ed.; Wiley-Blackwell: Oxford, 2008CrossRefGoogle Scholar
  5. 2.(e)
    MicroProcess Engineering, Hessel, V.; Renken, A.; Schouten, J. C.; Yoshida, J., Eds.; Wiley-Blackwell: Oxford, 2009.Google Scholar
  6. 2.
    For selected recent reviews on continuous-flow/microreactor chemistry, see: (a) Wiles, C. Watts, P. Green Chem. 2012, 14, 38–54CrossRefGoogle Scholar
  7. 2.(b)
    Noël, T.; Buchwald, S. L. Chem. Soc. Rev. 2011, 40, 5010–5029CrossRefGoogle Scholar
  8. 2.(c)
    Baumann, M.; Baxendale, I. R.; Ley, S. V. Mol. Diversity 2011, 15, 613–630CrossRefGoogle Scholar
  9. 2.(d)
    Hartman, R. L.; McMullen, J. P.; Jensen, K. F. Angew. Chem., Int. Ed. 2011, 50, 7502–7519CrossRefGoogle Scholar
  10. 2.(e)
    Wiles, C.; Watts, P. Chem. Commun. 2011, 47, 6512–6535.CrossRefGoogle Scholar
  11. 2.(f)
    Wegner, J.; Ceylan, S.; Kirschning, A. Chem. Commun. 2011, 47, 4583–4592.CrossRefGoogle Scholar
  12. 2.(g)
    Yoshida, J. I.; Kim, H.; Nagaki, A. ChemSusChem 2011, 4, 331–340.CrossRefGoogle Scholar
  13. 2.(h)
    Wegner, J.; Ceylan, S.; Kirschning, A. Adv. Synth. Catal. 2012, 354, 17–57CrossRefGoogle Scholar
  14. 2.(i)
    Jimenez-Gonzalez, C.; Poechlauer, P.; Broxterman, Q. B.; Yang, B. S.; am Ende, D.; Baird, J.; Bertsch, C.; Hannah, R. E.; Dell’Orco, P.; Noorman, H.; Yee, S.; Reintjens, R.; Wells, A.; Massonneau, V.; Manley, J. Org. Process Res. Dev. 2011, 15, 900–911.CrossRefGoogle Scholar
  15. 3.
    For selected examples of API synthesis in flow: (a) Hopkin, M. D.; Baxendale, I. R.; Ley, S. V. Chem. Commun. 2010, 46, 2450–2452CrossRefGoogle Scholar
  16. 3.(b)
    Grongsaard, P.; Bulger, P. G.; Wallace, D. J.; Tan, L.; Chen, Q.; Dolman, S. J.; Nyrop, J.; Hoerrner, R. S.; Weisel, M.; Arredondo, J.; Itoh, T.; Xie, C.; Wen, X.; Zhao, D.; Muzzio, D. J.; Bassan, E. M.; Shultz, C. S Org. Process Res. Dev. 2012, 16, 1069–1081CrossRefGoogle Scholar
  17. 3.(c)
    Gustafsson, T.; Sörensen, H.; Ponten, F. Org. Process Res. Dev. 2012, 16, 925–929CrossRefGoogle Scholar
  18. 3.(d)
    Johnson, M. D.; May, S. A.; Calvin, J. R.; Remacle, J.; Stout, J. R.; Diseroad, W. D.; Zaborenko, N.; Haeberle, B. D.; Sun, W. M., Miller, M. T.; Brennan, J. Org. Process Res. Dev. 2012, 16, 1017–1038CrossRefGoogle Scholar
  19. 3.(e)
    Hopkin, M. D.; Baxendale, I. R.; Ley, S. V. Org. Biomol. Chem. 2013, 11, 1822–1839CrossRefGoogle Scholar
  20. 3.(f)
    Gutmann, B.; Cantillo, D.; Kappe, C. O. Angew. Chem. Int. Ed. 2015, 54, 6688.CrossRefGoogle Scholar
  21. 4.(a)
    Della-Vechia, L.; Reichard, B.; Glasnov, T.; Miranda, L. S. M.; Kappe, C. O.; Souza, R. O. M. A. Org. Biomol. Chem. 2013, 11, 6806–6813CrossRefGoogle Scholar
  22. 4.(b)
    Pinho, V. D.; Gutmann, B.; Miranda, L. S. M.; Souza, R. O. M. A.; Kappe, C. O. J. Org. Chem. 2014, 79, 1555–1562.CrossRefGoogle Scholar
  23. 5.(a)
    Ebhralm, O.; Mazanderano, A. H. Infect. Dis. Rep. 2013, 5, Suppl 1, e2Google Scholar
  24. 5.(b)
    Eholië, S. P.; Aossi, F. E.; Ouattara, I. S.; Bissagnënë, E.; Anglaret, X. J. Int. AIDS Soc. 2012, 15, 17334–17340.Google Scholar
  25. 6.
    Ghosh, A. K.; Dawsona, Z. L.; Mitsuya, H. Bioorg. Med. Chem. 2007, 15, 7576–7580.CrossRefGoogle Scholar
  26. 7.(a)
    Yu, R. H.; Polniaszek, R. P.; Becker, M. W.; Cook, C. M.; Yu, L. H. L. Org. Process. Res. Dev., 2007, 11, 972–980CrossRefGoogle Scholar
  27. 7.(b)
    Black, D. M.; Davis, R.; Doan, B. D.; Lovelace, T. C.; Millar, A.; Toczko, J. F.; Xie, S. Tetrahedron: Asymmetry, 2008, 19, 2015–2019Google Scholar
  28. 7.(c)
    Ghosh, A. K.; Kincaid, J. F.; Walters, D. E. J. Med. Chem. 1996, 39, 3278–3290CrossRefGoogle Scholar
  29. 7.(d)
    Ghosh, A. K.; Li, J.; Perali, R. S. Synthesis 2006, 3015–3018Google Scholar
  30. 7.(e)
    Ghosh, A. K.; Leshchenko, S.; Noetzel, M. J. Org. Chem. 2004, 69, 7822–7829CrossRefGoogle Scholar
  31. 7.(f)
    Ghosh, A. K.; Chen, Y. Tetrahedron Lett. 1995, 36, 505–508.CrossRefGoogle Scholar
  32. 8.(a)
    Quaedflieg, P. J. L. M.; Kesteleyn, B. R. R.; Wigerinck, P. B. T. P.; Goyvaerts, N. M. F.; Vijn, R. J.; Liebregts, C. S. M.; Kooistra, J. H. M. H.; Cusan, C. Org. Lett. 2005, 7, 5917–5920CrossRefGoogle Scholar
  33. 8.(b)
    Canoy, W. L.; Cooley, B. E.; Corona, J. A.; Lovelace, T. C.; Millar, A.; Weber, A. M.; Xie, S.; Zhang, Y. Org. Lett. 2008, 10, 1103–1106.CrossRefGoogle Scholar
  34. 9.(a)
    de Miranda, A. S.; Miranda, L. S. M.; Souza, R. O. M. A. Org. Biomol. Chem., 2013, 11, 3332–3336CrossRefGoogle Scholar
  35. 9.(b)
    de Miranda, A. S.; Miranda, L. S. M.; Souza, R. O. M. A. RSC Adv., 2014, 4, 13620–13625CrossRefGoogle Scholar
  36. 9.(c)
    de Miranda, A. S.; Gomes, J. C.; Rodrigues, M. T; Costa, I. C. R.; Almeida, W. P.; Lopes, R. O.; Miranda, L. S. M.; Coelho, F.; Souza, R. O. M. A. J. Mol. Cat. B: Enzymatic 2013, 91, 77–80.CrossRefGoogle Scholar
  37. 10.
    Khmelnitsky, Y. L.; Michels, P. C.; Cotterill, I. C.; Eissenstat, M.; Sunku, V.; Veeramaneni, V. R.; Cittineni, H.; Kotha, G. R.; Talasani, S. R.; Ramanathan, K. K.; Chitineni, V. K.; Venepalli, B. R. Org. Process. Res. Dev. 2011, 15, 279–283.CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó 2015

Authors and Affiliations

  • Raquel A. C. Leão
    • 1
  • Raquel O. de Lopes
    • 1
  • Marco A. de M. Bezerra
    • 1
  • Mauro N. Muniz
    • 2
  • Bruna B. Casanova
    • 2
  • Simone C. B. Gnoatto
    • 2
  • Grace Gosmann
    • 2
  • Laszlo Kocsis
    • 3
  • Rodrigo O. M. A. de Souza
    • 1
  • Leandro S. M. de Miranda
    • 1
  1. 1.Biocatalysis and Organic Synthesis Group, Chemistry InstituteUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil
  2. 2.Universidade Federal do Rio Grande do SulFaculty of PharmacyPorto AlegreBrazil
  3. 3.ThalesNano Inc. Zahony u. 7Faculty of PharmacyHungary

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