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9-Fluorenylmethyl chloroformate (Fmoc-Cl) as a useful reagent for the synthesis of pentafluorophenyl, 2,4,5-trichlorophenyl, pentachlorophenyl, p-nitrophenyl, o-nitrophenyl and succinimidyl esters of Nα-urethane protected amino acids

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Abstract

9-Fluorenylmethyl chloroformate has been demonstrated to be useful reagent for the synthesis of several commonly used activeesters of Fmoc-/Boc-/Z-amino acids. These include pentafluorophenyl, 2,4,5-trichlorophenyl, pentachlorophenyl, p-nitrophenyl, o-nitrophenyl, and succinimidyl esters. The method is simple, rapid and efficient. All the compounds made have been isolated as crystaline solids in good yield and optical purity. They were fully characterized by IR, and 1H NMR.

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References

  1. Jones, J., The Chemical Synthesis of Peptides, Clarendon Press, Oxford, 1991.

    Google Scholar 

  2. Jones, J. H., The Formation of Peptide Bond: A General Survey in The Peptides, in E. Gross and J. Meienhofer (eds), Academic Press, New York, Vol. 1, 1979, pp. 65.

    Google Scholar 

  3. Bodanszky, M., Principles of Peptide Synthesis, Springer-Verlag, Berlin, revised edn., 1993, p. 29.

    Google Scholar 

  4. Bodanszky, M., Catalysis of active esters in peptide synthesis, J. Protein Chem., 4 (1985) 69.

    Google Scholar 

  5. Albericio, F. and Carpino, L. A., Coupling Reagents and Activation in Methods in Enzymology by Fields G B, Academic Press, New York, 289, 1997, p. 104.

    Google Scholar 

  6. Llyod-Williams, P., Albericio, F. and Giralt, E., Chemical Approaches to the Synthesis of Peptides and Proteins, CRC Press, New York, 1997, p. 55.

    Google Scholar 

  7. Gutte, B., Peptides, Synthesis, Structures, and Applications, Academic Press, New York, 1995, p. 42.

    Google Scholar 

  8. Autherton, E. and Sheppard, R. C., Solid Phase Peptide Synthesis, A Practical Approach, IRL Press, Oxford, 1989, p. 75.

    Google Scholar 

  9. Benoiton, N. L., Houben-Weyl Methods of Organic Chemistry, Synthesis of Peptides and Peptidomimitics, in M. Goodman, A. Felix, L. Moroder and C. Toniolo (eds), New York, Vol. E 22a, 2002, p. 443.

  10. Bambino, F., Brownlee, R. T. C. and Chiu, F. C. K., Tetrahedron Lett., 32 (1991) 3407.

    Google Scholar 

  11. Kisfaludy, L., Low, M., Nyeki, O., Szirtes, T. and Schon, I., Leibigs Ann. Chem., (1973) 1421.

  12. Kisfaludy, L. and Schon, I., Synthesis (1983) 325.

  13. Pless, J. and Boissonnas, R. A., Helv. Chim. Acta, 46 (1963) 1609.

    Google Scholar 

  14. Sivanandaiah, K. M. and Gurusiddappa, S., Synthesis, 7 (1981) 565.

    Google Scholar 

  15. Johnson, B. J. and Treask, E. G., J. Org. Chem., 33 (1986) 4521.

    Google Scholar 

  16. Bodanszky, A., Bodanszky, M., Chandramouli, N., Kwei, J. Z., Martinez, J. and Tolle, J. C., J. Org. Chem., 45 (1980) 72.

    Google Scholar 

  17. Sandrin, E. and Boissonnas, R. A., Helv. Chim. Acta, 46 (1963) 1637.

    Google Scholar 

  18. Bayer, E., Jung, G. and Hagenmeier, H., Tetrahedron, 24 (1968) 4853.

    Google Scholar 

  19. Bodanszky, M., Tolle, J. C., Bednerek, A. and Schiller, P. W., Int. J. Pept. Protein Res., 7 (1981) 444.

    Google Scholar 

  20. Bodanszky, M. and Du Vigneand, V., Nature, 183 (1959) 1324.

    Google Scholar 

  21. Anderson, G. W., Zimmerman, J. E. and Callahan, F. M., J. Am. Chem. Soc., 85 (1963) 3039.

    Google Scholar 

  22. Anderson, G. W., Zimmerman, J. E. and Callahan, F. M., J. Am. Chem. Soc., 86 (1964) 1839.

    Google Scholar 

  23. Bodanszky, M., Active Esters in Peptide Synthesis in the Peptides, in E. Gross and J. Meienhofer (eds), Academic Press, New York, Vol. 1, 1979, p. 105.

    Google Scholar 

  24. Konig, W. and Geiger, R. G., Chem. Ber., 186 (1973) 3626.

    Google Scholar 

  25. Carpino, L. A., El-Faham, A., Minor, C. A. and Albericio, F., J. Chem. Soc., Chem. Commun., (1994) 201.

  26. Kim, S., Lee, J. I. and Kim, Y. G., J. Org. Chem., 50 (1985) 560.

    Google Scholar 

  27. Broadbent, B. W., Morley, J. W. and Stone, D. E. J., Chem. Soc., Chem Commun., (1967) 2632.

  28. Wolman, Y., Ladkany, D. and Frankel, M. J., J. Chem. Soc., Chem. Commun., (1967) 689.

  29. Green, M. and Berman, J., Tetrahedron Lett., 31 (1990) 5851.

    Google Scholar 

  30. Suresh Babu, V. V., Ananda, K. and Mathad, R. I., Lett. in Peptide Sci., 7 (2000) 239.

    Google Scholar 

  31. Pozdnev, V. F., Int. J. Pept. Protein Res., 40 (1992) 407.

    Google Scholar 

  32. Benoiton, N. L., Lee, Y. C. and Chen, F. M. F., Int. J. Pept. Protein Res., 42 (1993) 278.

    Google Scholar 

  33. Jaouadi, M., Selve, C., Dormoy, J. R., Castro, B. and Martinez, J., Tetrahedron Lett., 26 (1985) 1721.

    Google Scholar 

  34. Sheehan, J. C. and Hess, G. P., J. Am. Chem. Soc., 77 (1955) 1067.

    Google Scholar 

  35. Bodanszky, M. and Bodanszky, A., The Practice of Peptide Synthesis, Springer-Verlag, Berlin, 1984, pp. 113–121.

    Google Scholar 

  36. Schon, I. and Kisfaludy, L., Synthesis, (1986) 303.

  37. Carpino, L. A. and Han, G. Y., J. Am. Chem. Soc., 92 (1970) 5748.

    Google Scholar 

  38. Carpino, L. A. and Han, G. Y., J. Org. Chem., 37 (1972) 3404.

    Google Scholar 

  39. Carpino, L. A., Acc. Chem. Res., 20 (1987) 401.

    Google Scholar 

  40. Chang, C. D. and Meienhofer, J., Int. J. Pept. Protein Res., 11 (1978) 246.

    Google Scholar 

  41. Merette, S. A. M., Burd, A. P. and Deadman, J. J., Tetrahedron Lett., 40 (1999) 753.

    Google Scholar 

  42. Fmoc-L-Phe-Ala-OMe (Figure 1, R t value 16.62 min) and Fmoc-D-Phe-Ala-OMe (Figure 2, R t value 17.56 min); Shi-madzu CLASS-VP V6.1 HPLC using the mobile phase: −acetonitrile: water:: 50: 50; flow rate: −1.0 mL min−1; Column: – Merck RP-18, 250 × 4.0 mm; monitoring at 215 nm.

  43. H NMR for Fmoc-Phe-Ala-OMe; (δ, ppm in CDCl3): 1.2–1.3 (3H, d), 3.0 (2H, d), 3.6 (3H, s), 4.1 (1H, t), 4.2–4.5 (4H, m), 5.3 (1H, br), 6.2 (1H, br), 7.0-7.8 (13H, ArH). Fmoc-D-Phe-Ala-OMe; (δ, ppm in CDCl3): 1.2– 1.3 (3H, d), 3.0 (2H, d),3.7 (3H, s), 4.2 (1H, t), 4.2–4.5 (4H, m), 5.3 (1H, br), 6.2 (1H,br), 7.0–7.8 (13H, ArH).

  44. Fletcher, G. A. and Jones, J. H., Int. J. Pept. Protein Res., 4 (1972) 347.

    Google Scholar 

  45. Fields, G. B. and Noble, R. L., Int. J. Pept. Protein Res., 35 (1990) 161.

    Google Scholar 

  46. Thomas, D. W. and Jones, J. H., Int. J. Pept. Protein Res., 25 (1985) 213.

    Google Scholar 

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Authors and Affiliations

  1. Department of Studies in Chemistry, Central College Campus, Dr. B. R. Ambedkar Veedhi, Bangalore University, Bangalore, India

    Subramanyam J. Tantry & Vommina V. Suresh Babu

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  1. Subramanyam J. Tantry
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  2. Vommina V. Suresh Babu
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Tantry, S.J., Suresh Babu, V.V. 9-Fluorenylmethyl chloroformate (Fmoc-Cl) as a useful reagent for the synthesis of pentafluorophenyl, 2,4,5-trichlorophenyl, pentachlorophenyl, p-nitrophenyl, o-nitrophenyl and succinimidyl esters of Nα-urethane protected amino acids. Int J Pept Res Ther 10, 655–662 (2003). https://doi.org/10.1023/B:LIPS.0000049132.01206.4c

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  • DOI: https://doi.org/10.1023/B:LIPS.0000049132.01206.4c

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