• Carpino, L.A. and Han, G.Y., J. Org. Chem. , 37 : 3404 (1972).
• Chang, C.D., Waki, M., Ahmad, M., Meienhofer, J., Lundell, E.O. and Haug, J.D., Int. J. Peptide Protein Res. , 15 : 59 (1980).
• Reagent for the protection of amino groups in peptide synthesis (see Appendix 6) as their 9-fluorenylmethoxycarbonyl (Fmoc) derivatives: J. Org. Chem., 37, 3404 (1972); J. Am. Chem. Soc., 96, 4987 (1974); 99, 7363 (1977). Review: Acc. Chem. Res., 20, 401 (1987). They are particularly applicable in solid-phase peptide synthesis. The stability of Fmoc-protected amino acids to acidic conditions permits their conversion in many cases to the acid chlorides as active intermediates for peptide coupling, resistant to racemization, in contrast to other protected amino acid chlorides. For a review of peptide synthesis via amino acid halides, see: Acc. Chem. Res., 29, 268 (1996).
• Cleavage of the Fmoc group occurs under mildly basic conditions:
• Limited use has also been made in the protection of alcohols as 9-fluorenylmethyl carbonates, rapidly cleaved by triethylamine: J. Chem. Soc., Chem. Commun., 672 (1982).
• Ethanolamine: J. Am. Chem. Soc., 92, 5748 (1970); J. Org. Chem., 37, 3404 (1972). Piperidine: J. Org. Chem., 52, 1197 (1987); applicable to solid-phase peptide synthesis.
•
In the presence of triethylamine, reacts with Pentafluorophenol, A15574, to give the PFP carbonate, a useful active ester for the preparation of Fmoc-amino acids. Moreover, the active PFP ester of the protected amino acid can be obtained by in situ DCC coupling with the liberated PFP: Synthesis, 303 (1986).•
TBAF in DMF; rapid reaction at room temperature: Tetrahedron Lett., 28, 6617 (1987). For both the deblocking of Fmoc-protected amino acids and for the removal of excess reagent during the protection step, 4-(Aminomethyl)piperidine, L11577, has been recommended: J. Org. Chem., 51, 3732 (1986); 55, 721 (1990), particularly in conjunction with Fmoc-protected acid chlorides as the active species. Even better results have been obtained with Tris(2-aminoethyl)amine, B21789, in this type of chemistry: J. Org. Chem., 55, 1673 (1990).
Corrosive (C)
Harmful (X)