Maurice-Bernard Fleury

A biomimetic electrocatalytic system for the atom-economical chemoselective synthesis of secondary amines.

A facile one-pot oxidation-imine formation-reduction route to secondary amines can be achieved electrolytically from primary amines. This atom-economical 1(ox)-mediated sequence, leaving ammonia as the sole byproduct, allows the rapid chemoselective synthesis of secondary amines, at both ambient temperature and pressure.

Novel 1,4-benzoxazine derivatives of pharmacological interest. Electrochemical and chemical syntheses

Abstract The reaction of electrochemically or chemically generated orthoquinones with aminoalcohols, in methanol, affords a convenient route to novel 1,4-benzoxazine derivatives. Some of these compounds are found to possess interesting pharmacological properties.

The neuroprotective activity of 8-alkylamino-1,4-benzoxazine antioxidants.

Antioxidant 8-alkylamino-1,4-benzoxazines, (R,S)-(3-tert-butyl-8-phenylethylamino-3,4-dihydro-2H-1,4-benzoxazin-5-yl) (phenyl) methanone (S 24429) and (R,S)-(3-cyclopentyl-8-benzylamino-3,4-dihydro-2H-1,4-benzoxazin-5-yl) (phenyl) methanone (S 24718), were prepared according to a two-step one-pot electrochemical procedure. These compounds had been selected from a previous study of structure/activity. Both compounds (1-100 microM) prevented the fall in ATP levels caused by 24 h of hypoxia in astrocytes. Both compounds (1 and 10 mg/kg i.p.) were powerful neuroprotective agents in protecting against the lesions induced by 15 microg S-bromo-willardiine injected into the cortex or white matter of 5-day old mice pups. In contrast, exifone, an antioxidant compound, was inactive at these doses. S 24429 and S 24718 appear to be novel neuroprotective agents, which are effective in a model of brain damage mimicking the lesions underlying cerebral palsy.

Reactivity of substituted 1,2-dithiole-3-thiones with sodium ethanethiolate: a convenient route to a novel heterocycle

Abstract Sodium ethanethiolate reacts at the S-2 position of substituted 1,2-dithiole-3-thiones to give various products depending on the substiuents at the C-4 and C-5 positions. In particular, the presence of a pyrimidinyl substituent induces some noticeable changes in the reaction pathway, yielding a novel heterocycle whose synthesis has not been previously reported.

Studies of the reaction of 1,2-dithiole-3-thiones with nucleophiles

Abstract Substituted 1,2-dithiole-3-thiones react with nucleophiles (alkoxides, thiolates) to give various reaction products depending on the nucleophiles and on the substituents on the 1,2-dithiole-3-thione ring. The mechanistic aspects of these reactions are discussed.

Metabolism of oltipraz and glutathione reductase inhibition

A decrease in glutathione reductase (GR) activity was observed in Schistosoma mansoni isolated from oltipraz(OPZ)-treated mice. Yeast and Schistosoma mansoni GR-activity was inhibited by OPZ derivatives only. These OPZ-derivatives showed in vitro schistosomicidal activity. Using yeast GR and dithiolium salts of OPZ, time-dependent inactivation and gel chromatography experiments revealed irreversible inhibition dependent on the redox state of the enzyme. Binding of radiolabelled ([3H]7-methyl-8-methylthio-pyrrolo[1,2-a]pyrazine disulphide 1b) obtained from OPZ was observed using exclusion chromatography and equilibrium dialysis. These results indicate that GR can be considered as the target of schistosomicidal activity of OPZ. The lack of inhibitory activity of OPZ and dithiole-thione analogues, and the potent activity of the corresponding pyrrolo-pyrazine derivatives, is consistent with the hypothesis that OPZ is a pro-drug.

Use of Methylene Chloride as a C1 Unit in N,N-Dialkylaminomethylation Reaction

Abstract Mannich products have been isolated in good yields with methylene chloride as a C1 unit, instead of formaldehyde. It is evidenced that, contrary to previous understanding, a high pressure procedure is not necessary required and that the methylene bisamines function as intermediates.

Toward an understanding of the schistosomicidal effect of 4-methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione (oltipraz).

In order to gain an interpretation of the schistosomicidal effect of 4-methyl 5-(2-pyrazinyl)-1,2-dithiole-3-thione (oltipraz), chemical, electrochemical and enzymatic hypotheses are discussed from a pharmacological standpoint. The enzymatic hypothesis is in good agreement with experimental results which ascertain that oltipraz behaves as a prodrug.

Electrochemical reduction of pristinamycin IA and related streptogramins in aqueous acidic medium.

Abstract The electrochemical reduction of the picolinoyl residue of pristinamycin I A and related streptogramins was performed at a mercury cathode, in aqueo

Synthesis of novel orthoalkylaminophenol derivatives as potent neuroprotective agents in vitro

A series of orthoalkylaminophenol derivatives was synthesized and tested in vitro with respect to their neuroprotective effect. Some of these compounds exhibited a potent antioxidant activity close to that of standard alpha-tocopherol.