Nα-Alloc temporary protection in solid-phase peptide synthesis. The use of amine–borane complexes as allyl group scavengers

(Note: The full text of this document is currently only available in the PDF Version )

Paloma Gomez-Martinez, Michèle Dessolin, François Guibé and Fernando Albericio


Abstract

The use of a combination of amine–borane complexes and soluble palladium catalyst allows the fast deprotection of allyl carbamates under near-to-neutral conditions and without any side-formation of allylamine. Preliminary experiments indicate that palladium catalyst–amine–borane systems seem ideally suited for removal of Nα-Alloc terminal groups during solid phase peptide synthesis according to the N[hair space] α-Alloc temporary protection strategy.


References

  1. G. B. Fields, Z. Tian and G. Barany, in Synthetic Peptides, A User's Guide, ed. G. A. Grant, W. H. Freeman and Company, New York, 1992, p. 77 Search PubMed.
  2. P. Lloyd-Williams, F. Albericio and E. Giralt, Chemical Approaches to the Synthesis of Peptides and Proteins, CRC Press, Boca Raton, New York, 1997 Search PubMed.
  3. For a recent illustration of the use of a sulfonyl group for Nαtemporary protection in SPPS see: S. C. Miller and T. S. Scanlan, J. Am. Chem. Soc., 1998, 120, 2690 Search PubMed see also: L. A. Carpino, D. Ionescu, A. El-Faham, P. Henklein, H. Wenschuh, M. Bienert and M. Beyermann, Tetrahedron Lett., 1998, 39, 241 CrossRef CAS.
  4. H. Kunz and H. Waldmann, Angew. Chem., Int. Ed. Engl., 1984, 23, 71 CrossRef; H. Kunz and C. Unverzagt, Angew. Chem., Int. Ed. Engl., 1984, 23, 436 CrossRef.
  5. For a review see: F. Guibé, Tetrahedron, 1998, 54, 2967 Search PubMed.
  6. For recent references see: O. Seitz and H. Kunz, J. Org. Chem., 1997, 62, 813 Search PubMed; O. Seitz, Tetrahedron Lett., 1999, 40, 4161 CrossRef CAS.
  7. N. Thieriet, J. Alsina, E. Giralt, F. Guibé and F. Albericio, Tetra-hedron Lett., 1997, 38, 7275 Search PubMed.
  8. O. Dangles, F. Guibé, G. Balavoine, S. Lavielle and A. Marquet, J. Org. Chem., 1987, 52, 4984 CrossRef CAS.
  9. A solution phase synthesis in aqueous medium of di-, tri- and tetrapeptides based on temporary Alloc protection and the use of water soluble phosphine ligands for palladium has been reported by Genêt and co-workers (S. Lemaire-Audoire, M. Savignac, E. Blart, J.-M. Bernard and J.-P. Genêt, Tetrahedron Lett., 1997, 38, 2955) Search PubMed.
  10. A. Merzouk, F. Guibé and A. Loffet, Tetrahedron Lett., 1992, 33, 477 CrossRef CAS.
  11. H. Kunz and J. März, Angew. Chem., Int. Ed. Engl., 1988, 27, 1375 CrossRef.
  12. J. P. Genêt, E. Blart, M. Savignac, S. Lemeune, S. Lemaire-Audoire and J.-M. Bernard, Synlett, 1993, 680 CrossRef CAS.
  13. R. Beugelmans, S. Bourdet, A. Bigot and J. Zhu, Tetrahedron Lett., 1994, 35, 4349 CrossRef CAS; R. Beugelmans, L. Neuville, M. Bois-Choussy, J. Chastanet and J. Zhu, Tetrahedron Lett., 1995, 36, 3129 CrossRef CAS.
  14. M. Dessolin, M.-G. Guillerez, N. Thieriet, F. Guibé and A. Loffet, Tetrahedron Lett., 1995, 36, 5741 CrossRef CAS.
  15. Selected references: H. C. Brown, M. Zaidlewicz and P. V. Dalvi, Organometallics, 1998, 17, 4202 Search PubMed; A. M. Salunkhe and E. R. Burkhardt, Tetrahedron Lett., 1997, 38, 1519 CrossRef CAS; G. C. Andrews and T.-C. Crawford, Tetrahedron Lett., 1980, 21, 693 CrossRef; A. Pelter and K. Smith, in Comprehensive Organic Chemistry, ed. D. H. R. Barton and W. D. Ollis, Pergamon Press, Oxford, 1979, vol. 3, pp. 699 and 728 CrossRef CAS.
  16. Reviews: I. Beletskaya and A. Pelter, Tetrahedron, 1997, 53, 4957 Search PubMed; K. Burgess and M. J. Ohlmeyer, Chem. Rev., 1991, 91, 1179 CrossRef CAS.
  17. In the presence of 2 mol% of Pd(PPh3)4, half-reaction times of less than 5 min at room temperature were found, in our laboratory, for the conversion of the Alloc derivatives of morpholine or N-methylbenzylamine to the corresponding allylamines. As a comparison, the half-conversion times for Alloc-Val-OMe or Alloc-Tyr(O-t-Bu)-OMe under similar conditions are approximatively 1 h.
  18. N. Thieriet, P. Gomez-Martinez and F. Guibé, Tetrahedron Lett., 1999, 40, 2505 CrossRef CAS.
  19. The concentration of reactants in these control experiments were the same as those used in the deprotection of Nα-Alloc derivatives 3 and 4..
  20. A. Loffet and H. X. Zhang, Int. J. Peptide Protein Res., 1993, 42, 346 CAS.
  21. M. Green and J. Berman, Tetrahedron Lett., 1990, 31, 5851 CrossRef CAS.
  22. J. M. Stewart and J. D. Young, Solid Phase Peptide Synthesis, Pierce Chemical Company, 2nd edn., 1984, p. 63 Search PubMed.
Click here to see how this site uses Cookies. View our privacy policy here.