New peptidic compounds, having peptide chains linked to bi- and tricyclic heterocycles (peptide-heterocycle hybrids), have been synthesized. The heterocyclic components are derivatives of partially reduced isoquinoline and pyrido[1,2-b]isoquinoline bearing α,β-unsaturated carbonyl functionalities. The heterocyclic compounds have been used as acylating agents in coupling reactions with short N-unprotected peptides. Based on our interest on potential calpain inhibitors, we have used short (2-4 amino acids) peptides with hydrophobic amino acids of the two enantiomeric series. We report preliminary studies on the inhibition of calpain, with some compounds having IC50 values in the nanomolar range.

The single crystal X-ray diffraction structure of (-)-pentafluorophenyl(Z,S,S)-2-(6-oxo-1,3,4,6,11,11a-hexahydro-2H-pyrido[1, 2-b]isoquinolin-11-yliden)acetate (1) is reported. We have found that the crystal packing of the α,β-unsaturated-γ-amino acid derivative 1 is mainly determined by the interaction between the two aromatic rings, namely the benzenic type and the pentafluorinated ring. The crystal packing of 1 shows a herringbone (zig-zag) structure, that is quite typical of aromatic compound with intermolecular arene-arene interactions. The benzenic and the fluorinated phenyl rings in 1 are in a matched face-to-face arrangement. The origin of this interaction can be ascribed to a favourably quadrupolar interaction between both types of aromatic ring. The results reported in the present paper indicate that the pentafluorophenyl ester functionality can be a useful building block in crystal engineering. © 2002 Elsevier Science B.V. All rights reserved.

1.1′-Biphenyl derivatives with amino acid/peptide substitution at C(2) and C(2′) ('peptide-biphenyl hybrids', 6-8) have been prepared by direct N-acylation of amino acid/peptide derivatives with 1,1′-biphenyl-2,2′-dicarbonyl dichloride (5). Both conformers, which arise from the rotation around the aryl-aryl bond, have been detected by 1H-NMR spectroscopy. Single atropisomers of each 6 ((R)-configuration at the stereogenic axis) and 7 ((S)-configuration at the stereogenic axis) have been obtained in quantitative yield by slow evaporation of methanolic solutions. The procedures are dynamic atropselective resolutions (asymmetric transformations of the second kind). The crystal structures of the peptide-biphenyl hybrids 6 and 7 show highly ordered molecular and supramolecular structures with extensive intramolecular and intermolecular H-bonding.

The palladium(0)-catalyzed reaction of derivatives of γ-amino-α,β-unsaturated esters bearing an N-(2-iodobenzoyl) substituent results in an intramolecular Heck reaction, the outcome of which depends on the structure of the substrate as well as on the experimental conditions. The methodology developed has been applied to the efficient syntheses of chiral isoquinoline and pyrido[1,2-b]isoquinoline derivatives.

The surface properties of sepiolite were investigated by inverse gas chromatography. It is shown that the value of the dispersive component change uniformly with temperature, while the values obtained for the parameters KA and KD indicate an acidic character for the sepiolite surface. © 1991 Friedr. Vieweg & Sohn Verlagsgesellschaft mbH.