The complex of a bivalent derivative of galanthamine with torpedo acetylcholinesterase displays drastic deformation of the active-site gorge: implications for structure-based drug design

Bifunctional derivatives of the alkaloid galanthamine, designed to interact with both the active site of the enzyme acetylcholinesterase (AChE) and its peripheral cation binding site, have been assayed with Torpedo californica AChE (TcAChE), and the three-dimensional structures of their complexes with the enzyme have been solved by X-ray crystallography. Differences were noted between the IC(50) values obtained for TcAChE and those for Electrophorus electricus AChE. These differences are ascribed to sequence differences in one or two residues lining the active-site gorge of the enzyme. The binding of one of the inhibitors disrupts the native conformation of one wall of the gorge, formed by the loop Trp279-Phe290. It is proposed that flexibility of this loop may permit the binding of inhibitors such as galanthamine, which are too bulky to penetrate the narrow neck of the gorge formed by Tyr121 and Phe330 as seen in the crystal structure.     

Structures de l'odyendane et l'odyendene deux nouveaux quassinoides d'odyendea gabonensis (pierre) engl. Simaroubacees.

From the trunk bark of Odyendea gabonensis (Pierre) Engl. Simaroubaceae, two-new quassinoids have been isolated : Odyendane and Odyendene. Their structures were established from spectral data and X-Ray diffraction analysis.     

New Synthetic Route to Pummerer's Ketone

Pummerer's ketone 1 is obtained with an overall yield of 55 % by the following sequence: Claisen rearrangement of an arylcyclohexylether 3; allylic oxidation of the methylcycloalkylphenolic derivative 4b, then spontaneous cyclisation during demethylation to give 2. 1 is obtained by dehydrogenation of 2. NMR data agree with a cis stereochemistry at C_4a and C _9b.     

Synthesis and Separation of New Dibenz[b,d]azonine Atropisomers

A synthesis of the dibenz[b,d]azonine atropisomers (14) from 2-phenylbenzoic acid is described. This heterocycle belongs to a new series of biaryl compounds with potential antitubulin activity.     

Stereoselective synthesis of new spirobenzodihydropyrancyclohexanes

A stereoselective synthesis of unknown spirobenzodihydropyrancyclohexanes is described starting from arylcyclohexenes alkylated and cyclized via a coumarin intermediate and leading to new amino derivatives which are rigid analogs of dopamine.     

Biaryles dissymétriques par diformylation et aromatisation de cyclohexén-2 ones.

The classical procedure of formylation of ketones is reinvestigated in order to provide a synthetic route to unsymmetrical biaryls from cyclohexenones.     

Etudes en série indolique: VII Synthèse de nouveaux pyridocarbazoles obtenus par photocyclisation de (β-indolyl)-1 (pyridyl)-2 acrylonitriles

The photocyclization of 2-(3-indolyl)-3-(3-pyridyl)propenenitrile yields pyrido[a]carbazoles which represent intermediates to the original pentacyclic skeletons; the new indolopyridoquinoxaline 8 constitutes a structural analog of the alkaloid eburnamonin.