Merrifield Resin
(Chloromethyl Resin)

Merrifield resin was designed for anchoring [1-5] protected amino acids by nucleophilic displacement of chlorine [6] to give resin-bound benzyl esters. Following a sequence of amino acid coupling reactions, the peptide is typically cleaved from the resin by treatment with HF or trifluoromethanesulfonic acid (TFMSA).  

Base-induced cleavages of peptides from Merrifield resin have also been reported [7,8]. Cleavage of ester anchoring groups may also be accomplished by transesterication under either basic [9-11] or acidic [12] conditions. Protected peptide segments have been cleaved by ammonolysis [13] or hydrazinolysis [14]. Anchoring ester linkages may also be cleaved reductively using diisobutylaluminum hydride, resulting in release of alcohols from the support [15].

References

1. Merrifield, R. B. J Am Chem Soc 1963, 85, 2149
2. Gutte, B. et al. J Biol Chem 1971, 246, 1922
3. Barany, G. et al. The Peptides, Vol 2. New York: Academic Press, 1979, pp 1-284.
4. Merrifield, R. B. Peptides: Synthesis, Structures and Applications. San Diego: Academic Press, 1995, pp 93-169.
5. Fields, G. B. et al. Synthetic Peptides: A User's Guide. New York: WH Freeman, 1992, pp 77-183.
6. Gisin, B. F. Helv Chim Acta 1973, 56, 1476
7. Marshall, G. R. et al. Biochemistry 1965, 4, 2394
8. Answer, M. K. et al. Tetrahedron Lett 1992, 33, 3121
9. Frennette, R. et al. Tetrahedron Lett 1994, 35, 9177-9180
10. Tortolani, D. R. et al. Tetrahedron Lett 1996, 37, 5687
11. Charnoin, S. et al. Tetrahedron Lett 1998, 39, 4175
12. Marquis, S. et al. Tetrahedron Lett 1996, 37, 5491
13. Blake, J. et al. Int J Peptide Protein Res 1971, 3, 185
14. Kessler, W. et al. Helv Chim Acta 1966, 49, 1330
15. Kurth, M. J. et al. J Org Chem 1994, 59, 5862