p-Nitrobenzyloxycarbonyl (pNZ) as a temporary Na-protecting group in orthogonal solid-phase peptide synthesis - Avoiding diketopiperazine and aspartimide formation

European Journal of Organic Chemistry

Volumn , Issue 14, 2005, Pages 3031-3039

  Isidro Llobet, Albert ^a   Guasch Camell, Judit ^a   Álvarez, Mercedes ^a   Albericio, Fernando ^a  

^a UNIVERSITY OF BARCELONA   (Spain)

Author keywords

Amino protecting group; Combinatorial chemistry; Nitro reduction; PNZ group in SPPS; Side reactions; SnCl2 reduction

Indexed keywords

EID: 22544445896     PISSN: 1434193X     EISSN: None     Source Type: Journal    
DOI: 10.1002/ejoc.200500167     Document Type: Article

References (79)

1. a) R. B. Merrifield, J. Am. Chem. Soc. 1963, 85, 2149;
2. b) R. B. Merrifield, Angew. Chem. Int. Ed. Engl. 1985, 24, 799;
3. c) R. B. Merrifield, Science 1986, 232, 341.
4. S. Lien, H. B. Lowman, Trends Biotechnol. 2003, 21, 556.
5. a) A. Loffet, J. Pept. Sci. J. Peptide Sci. 2002, 8, 1;
6. b) T. Bruckdorfer, O. Marder, F. Albericio, Current Pharm. Biotech. 2004, 5, 29.
7. a) P. Lloyd-Williams; F. Albericio; E. Giralt, Chemical Approaches to the Synthesis of Peptides and Proteins, CRC, Boca Raton, FL, USA, 1997;
8. b) T. S. Yokum, G. Barany, in: Solid-phase Synthesis. A Practical Guide, Marcel Dekker Inc., New York, USA, 2000, pp. 79-102;
9. c) G. B. Fields, J. L. Lauer-Fields, R.-q. Liu, G. Barany, in: Synthetic Peptides: A User's Guide (Eds.: G. A. Grant), 2nd ed., W. H. Freeman & Co., New York, 2001, pp. 93-219;
10. d) M. Goodman, A. Felix, L. A. Moroder, C. Toniolo (Eds.), Houben-Weyl, vol. E22a-e ("Synthesis of Peptides and Peptidomimetics"), Georg Thieme Verlag, Stuttgart, Germany, 2002.
11. W. C. Chan; P. D. White (Eds.), Fmoc Solid Phase Peptide Synthesis, Oxford University Press, Oxford, UK, 2000.
12. The orthogonal concept is based on the use of independent classes of protecting groups, removed by different mechanisms so that they may be removed in any order and in the presence of all other types of groups, a) G. Barany, R. B. Merrifield, J. Am. Chem. Soc. 1977, 99, 7363;
13. b) G. Barany, F. Albericio, J. Am. Chem. Soc. 1985, 107, 4936.
14. F. Albericio, Biopolymers 2000, 55, 123.
15. a) F. H. Carpenter, D. T. Gish, J. Am. Chem. Soc. 1952, 74, 3818;
16. b) D. T. Gish, F. H. Carpenter, J. Am. Chem. Soc. 1953, 75, 950.
17. a) J. E. Shields, F. H. Carpenter, J. Am. Chem. Soc. 1961, 83, 3066;
18. b) M. D. Hocker, C. G. Caldwell, R. W. Macsata, M. H. Lyttle, Pept. Res. 1995, 8, 310;
19. c) S. Peluso, P. Dumy, C. Nkubana, Y. Yokokawa, M. Mutter, J. Org. Chem. 1999, 64, 7114.
20. a) P. Romanovskis, A. F. Spatola, J. Pept. Res. 1998, 52, 356;
21. b) M. Royo, J. Farrera-Sinfreu, L. Solé, F. Albericio, Tetrahedron Lett. 2002, 43, 2029.
22. a) M. D. Bachi, J. Ross-Peterson, J. Chem. Soc., Chem. Commun. 1974, 12;
23. b) R. R. Chauvette, P. A. Pennington, J. Med. Chem. 1975 18, 403;
24. c) S. R. Lammert, A. I. Ellis, R. R. Chauvette, S. Kukolja, J. Org. Chem. 1978, 43, 1243;
25. d) K. Fukase, H. Tanaka, S. Torii, S. Kusumoto, Tetrahedron Lett. 1982, 23, 885;
26. e) R. Balasuriya, S. J. Chandler, M. J. Cook, Tetrahedron Lett. 1983, 24, 1385;
27. f) S. Hashiguchi, H. Natsugari, M. Ochiai, J. Chem. Soc., Perkin Trans. 1 1988, 2345;
28. g) M. Namikoshi, B. Kundu, K. L. Rinehart, J. Org. Chem. 1991, 56, 5464.
29. M. Tessier, F. Albericio, E. Pedroso, A. Grandas, R. Eritja, E. Giralt, C. Granier, J. Van-Rietschoten, Int. J. Pept. Protein Res. 1983, 22, 125.
30. For a broad discussion of this subject, see: L. J. Cruz, N. G. Beteta, A. Ewenson, F. Albericio, Org. Process Res. Dev. 2004, 8, 920.
31. Although the existence of this side reaction was not mentioned, Fmoc-N3 was already proposed as an alternative to the chloroformate in the seminal papers of Carpino and Han: L. A. Carpino, G. Y. Han, J. Am. Chem. Soc. 1970, 92, 5748
32. and L. A. Carpino, G. Y. Han, J. Org. Chem. 1972, 37, 3404.
33. 2 should lead to the p- aminobenzyloxycarbonyl derivative, which liberates the free amine by the same mechanism as pNZ. However, in our hands this azide derivative gave substantially worse results than pNZ. a) B. Loubinoux, P. Gerardin, Tetrahedron Lett. 1991, 32, 351;
34. b) R. J. Griffin, E. Evers, R. Davison, A. E. Gibson, D. Layton, W. J. Irwin, J. Chem. Soc., Perkin Trans. 1 1996, 1205.
35. J.-F. Wen, W. Hong, K. Yuan, T. C. W. Mak, H. N. C. Wong, J. Org. Chem. 2003, 68, 8918, and references therein.
36. J. T. Manka, F. Guo, J. Huang, H. Yin, J. M. Farrar, M. Sienkowska, V. Benin, P. Kaszynski, J. Org. Chem. 2003, 68, 9574, and references therein.
37. a) W. Liao, C. F. Piskorz, R. D. Locke, K. L. Matta, Bioorg. Med. Chem. Lett. 2000, 10, 793;
38. b) X. Qian, O. Hindsgaul, Chem. Commun. 1997, 1059, and references therein.
39. a) A. A. Pletnev, Q. Tian, R. C. Larock, J. Org. Chem. 2002; 67, 9276;
40. b) M. Schlitzer, M. Böhm, I. Sattler, H.-M. Dahse, Bioorg. Med. Chem. 2000, 8, 1991.
41. [10]
42. a) E. Guibé-Jampel, M. Wakselman, Synth. Commun. 1982, 12, 219;
43. b) R. A. Scheurerman, D. Tumelty, Tetrahedron Lett. 2000, 41, 6531.
44. If aminium/uronium salt coupling methods are used, this neutralization step can be omitted. See synthesis of phospholipase A2 (18-23).
45. B. F. Gisin, R. B. Merrifield, J. Am. Chem. Soc. 1972, 94, 3102.
46. M. C. Khosla, R. R. Smeby, F. M. Bumpus, J. Am. Chem. Soc. 1972, 94, 3102.
47. [4a]
48. E. Pedroso, A. Grandas, X. de las Heras, R. Eritja, E. Giralt, Tetrahedron Lett. 1986, 27, 743.
49. a) K. Suzuki, K. Nitta, N. Endo, Chem. Pharm. Bull. 1975, 23, 222;
50. b) M. Gairi, P. Lloyd-Williams, F. Albericio, E. Giralt, Tetahedron Lett. 1990, 31, 7363.
51. a) K. Akaji, Y. Kiso, L. A. Carpino, J. Chem. Soc., Chem. Commun. 1990, 584;
52. b) K. Barlos, D. Gatos, W. Schaefer, Angew. Chem. Int. Ed. Engl. 1991, 30, 590;
53. c) C. Chiva, M. Vilaseca, E. Giralt, F. Albericio, J. Pept. Sci. 1999, 5, 131.
54. J. Alsina, E. Giralt, F. Albericio, Tetrahedron Lett. 1996, 37, 4195.
55. N. Thieriet, J. Alsina, E. Giralt, F. Guibé, F. Albericio, Tetrahedron Lett. 1997, 38, 7275.
56. [4a,26,27b,29]
57. For couplings without preactivation of the protected amino acid, phosphonium salts such as PyAOP are preferred to aminium/uronium salts, because the latter can give guanidinium formation. F. Albericio, J. M. Bofill, A. El-Faham, S. A. Kates, J. Org. Chem. 1998, 63, 9678.
58. a) J. P. Tam, M. W. Riemen, R. B. Merrifield, Pept. Res. 1988, 1, 6;
59. b) E. Nicolás, E. Pedroso, E. Giralt, Tetrahedron Lett. 1989, 30, 497;
60. c) Y. Yang, W. V. Sweeney, K. Schneider, S. Thornqvist, B. T. Hait, J. P. Tam, Tetrahedron Lett. 1994, 35, 9689;
61. d) R. Doelling, M. Beyermann, J. Haenel, F. Kernchen, E. Krause, P. Franke, M. Brudel, M. Bienert, J. Chem. Soc., Chem. Commun. 1994, 853;
62. e) J. L. Lauer, C. G. Fields, G. B. Fields, Lett. Pept. Sci. 1995, 1, 197;
63. f) J. Cebrian, V. Domingo, F. Reig, J. Pept. Res. 2003, 62, 238.
64. a) D. Delforge, M. Dieu, E. Delaive, M. Art, B. Gillon, B. Devreese, M. Raes, J. Van Beeumen, J. Remacle, Lett. Pept. Sci. 1996, 3, 89;
65. b) S. C. Vigil-Cruz, J. V. Aldrich, Lett. Pept. Sci. 1999, 6, 71.
66. a) A. Karlstroem, A. E. Unden, Tetrahedron Lett. 1995, 36, 3909;
67. b) A. Karlstroem, A. Unden, Int. J. Pept. Protein Res. 1996, 48, 305;
68. c) M. Mergler, F. Dick, B. Sax, P. Weiler, T. Vorherr, J. Pept. Sci. 2003, 9, 36;
69. d) M. Mergler, F. Dick, B. Sax, C. Staehelin, T. Vorherr, J. Pept. Sci. 2003, 9, 518.
70. a) M. Quibell, D. Owen, L. C. Peckman, T. Johnson, J. Chem. Soc., Chem. Commun. 1994, 20, 2343;
71. b) L. Urge, L. Otvos, Jr., Lett. Pept. Sci. 1995, 1, 207;
72. c) L. C. Packman, Tetrahedron Lett. 1995, 36, 7523.
73. The peptide backbone is through the β-carboxyl group of the Asp residue.
74. J. Lukszo, D. Patterson, F. Albericio, S. A. Kates, Lett. Pept. Sci. 1996, 3, 157.
75. E. Kaiser, R. L. Colescott, C. D. Bossinger, P. I. Cook, Anal. Biochem. 1970, 34, 595.
76. a) F. Albericio, G. Barany, Int. J. Pept. Protein Res. 1984, 23, 342;
77. b) F. Albericio, G. Barany, Int. J. Pept. Protein Res. 1984, 26, 92.
78. O. Kuisle, M. Lolo, E. Quiñoa, R. Riguera, Tetrahedron 1999, 55, 14807.
79. (Benzotriazol-1-yloxy)tris(pyrrolidino)phosphonium hexafluorophosphate (PyBOP) can also be used instead of PyAOP.