Synthesis, conformational study, and spectroscopic characterization of thecyclic C-alpha,C-alpha.-disubstituted glycine 9-amino-9-fluorenecarboxylicacid

A series of terminally blocked peptides (to the pentamer level) from L-Ala and the cyclic C-alpha,C-alpha-disubstituted Gly residue Afc and one Gly/Af c dipeptide have been synthesized by solution method and fully characterize d. The molecular structure of the amino acid derivative Boc-Afc-OMe and the dipeptide Boc-Afc-Gly-OMe were determined in the crystal state by X-ray di ffraction. In addition, the preferred conformation of all of the model pept ides was assessed in deuterochloroform solution by FT-IR absorption and H-1 -NMR. The experimental data favour the conclusion that the Afc residue tend s to adopt either the fully-extended (C-5) or a folded/helical structure. I n particular, the former conformation is highly populated in solution and i s also that found in the crystal state in the two compounds investigated. A comparison with the structural propensities of the strictly related C-alph a,C-alpha-disubstituted Gly residues Ac(5)c and D Phi g is made and the imp lications for the use of the Afc residue in conformationally constrained an alogues of bioactive peptides are briefly examined. A spectroscopic (UV abs orption, fluorescence, CD) characterization of this novel aromatic C-alpha, C-alpha-disubstituted Gly residue is also reported. Copyright (C) 1999 Euro pean Peptide Society and John Wiley & Sons, Ltd.