Jean Guilhem

Inhibition of human leukocyte elastase by functionalized N-aryl-3,3-dihalogenoazetidin-2-ones. Stereospecific synthesis and chiral recognition of dissymmetrically C3-substituted β-lactams

Abstract (3R)- and (3S)-N-(2-chloromethylphenyl)-3-bromo-3-fluoroazetidin-2-ones 2 were synthesized via the separation of diastereoisomeric phenylglycinol derivatives of the starting 2,3-dibromo-2-fluoropropanoic acid. Acidic hydrolysis of the hydroxyamides led to the chiral trihalogenopropanoic acids. Then, an expeditious four step synthesis provided the (3S)- and (3R)-azetidinones 2, both of which behaved as strictly irreversible inhibitors of HLE. The configuration of the bromofluorocarbon was shown to have a significant effect on the partition ratio: kcat/kinact=4.6 and 34.3 for (3S)- and 3R)-2, respectively.

New entries into theindolizino[8,7-b]indole ring system

Abstract Tetrahydro-β-carbolines2 and3 possessing a proton on nitrogen N-2 react with one molecule of activated alkyne to give, depending on the solvent, either enamines or heterocyclic derivatives ofindolizino[8,7-b]indole skeleton. The enamines obtained can be quantitatively transformed into the same skeleton. The application of acidic or basic catalysis determines the position of the double bond in the pyrrole ring as well as the nature of the substituents in positions 1,2,3 and 11b. Download : Download full-size image

Stereochemical Study of a Bradicardisant Benzazepine-Type Drug. X-Ray Structure of the Chloride Salt and High-Field NMR Study of the Stereochemistry in Solution

A chiral bradicardisant benzazepine‐type drug with an asymmetric carbon and a tertiary amino nitrogen was studied as the chloride salt. X‐ray analysis in the solid state of the salt formed upon protonation of the base shows the occurrence in the unit cell of two diastereomeric species with horseshoe‐shaped structures. NMR parameters were obtained for the base and for the protonated species in solution. A conformational study by 2D NOESY and ROESY NMR techniques led to the conclusion that conformations similar to the solid‐state structures were retained in solution. Over a wide range of pH, in particular in alkaline solution or under biological conditions, a conformation similar to that of the 1′(R) N(R) diastereomer is observed. The diastereomeric species 1′(R) N(R) and 1′(R) N(S) were clearly identified at low pH values with conformations similar to their solid‐state structures.

Binuclear Copper(II) Complexes of Cyclo-Bis Intercaland Receptors. Effect of the Ligand on the Crystal Structure and Complexation Properties

There has been considerable interest in metal complexes of binucleating ligands as models for the coordination environment of the active sites in binucleating metalloenzymes. Numerous synthetic systems, like di-copper or di-cobalt complexes, have been demonstrated to function as catalysts for the transformation (oxidation, hydrolysis) of organic substrates other than the ligand itself. The catalytic efficiency and the selectivity depends critically on the distance between the metallic centers, the conformation of the spacer and the stability of the complex.