Showing papers by "Carlos Cativiela published in 1998"

β-Turn Preferences Induced by 2,3-Methanophenylalanine Chirality†

Abstract: The model dipeptides RCO-l-Pro-c3Phe-NHMe, where c3Phe stands for each of the four cyclopropane analogues of phenylalanine (2,3-methanophenylalanine), have been studied in solution by using 1H NMR and FT-IR spectroscopy and in the solid state by using X-ray diffraction. The conformational behavior of these compounds has been compared to that of the analogous Ac3c and l- or d-Phe-containing dipeptides. When associated to proline, the cyclopropane residues in the so-called i + 2 position exhibit a marked tendency to β-folding in solution, even in DMSO. The type II β-turn is generally favored, but the βI/βII-turn ratio depends both on the experimental conditions (solvent, solution, or solid state) and on the chirality of the c3Phe moiety, which rigidly fixes the orientation of the phenyl ring with respect to the peptide backbone. The (2S,3S)c3Phe residue, analogous to l-Phe with the χ1 angle constrained to about 0°, is the most propitious to βI-folding in the i + 2 position of a putative β-turn.

A Versatile and Stereoselective Synthesis of (.+‐.)‐Epibatidine.

Abstract: A new synthesis of (±)-epibatidine has been achieved, involving a Diels–Alder cycloaddition of ( Z )-4-[5'-(2'-chloropyridylmethylene)]-2-phenyl-5(4 H )-oxazolone with Danishefsky's diene, and an intramolecular nucleophilic displacement in a trans 1,4-methanesulfonyloxycyclohexylamide derivative as key steps.

Resolution of (1R,2R)‐ and (1S,2S)‐Cyclic Constrained Phenylalanine Analogues (c6Phe). Conformations of (1R,2R)‐ and (1S,2S)‐c6Phe Containing Peptides.

Abstract: The enantiomerically pure (1R,2R)- and (1S,2S)-1-amino-2-phenylcyclohexane-1-carboxylic acids (c6Phe) 3a and 3b were synthesized in good yields by a resolution method described by Obrecht. This method involves the formation of the diastereoisomeric peptides 7a and 7b followed by chromatographic separation. The free (1R,2R)- and (1S,2S)-c6Phe amino acids (3a and 3b) were converted into appropriately protected phenylalanine analogues 10a and 10b for possible use in peptide synthesis. The conformational analysis, in solution, of these peptides revealed that dipeptide 3a shows an extended-type conformation, while dipeptide 3b shows a type I β-turn geometry. In addition, we have prepared the unsaturated peptides 11a and 11b and the structure of 11b, determined by X-ray analysis, also shows a type I β-turn conformation in the solid state. The NMR data of this dipeptide (11b) allowed the characterisation of the type I β-turn conformation in solution and established it to be similar to the solid state structure. These results suggest that c6Phe can be used as building blocks to stabilise type I β-turns or extended chains in peptides, depending on their absolute configurations.