Thierry Martens

Three-Component Synthesis of α-Branched Amines under Barbier-like Conditions

An array of alpha-branched amines has been prepared by using an expedient three-component Mannich-type reaction among organic halides, aldehyde derivatives, and amines. The experimental procedure, which is characterized by its simplicity, employs zinc dust for the in situ generation of organozinc reagents. We show that this Barbier-like protocol constitutes a useful entry to diarylmethylamines, 1,2-diarylethylamines, alpha- or beta-amino esters, benzylamines, and beta-arylethylamines.

A straightforward three-component synthesis of alpha-amino esters containing a phenylalanine or a phenylglycine scaffold.

A range of alpha-amino esters has been synthesized in good to high yields using a straightforward three-component reaction among preformed or in situ generated aromatic or benzylic organozinc reagents, primary or secondary amines, and ethyl glyoxylate. The procedure, which is characterized by its simplicity, allows the concise synthesis of esters bearing a phenylglycine or a phenylalanine scaffold.

Synthesis of small metallic Mg-based nanoparticles confined in porous carbon materials for hydrogen sorption

MgH2, Mg-Ni-H and Mg-Fe-H nanoparticles inserted into ordered mesoporous carbon templates have been synthesized by decomposition of organometallic precursors under hydrogen atmosphere and mild temperature conditions. The hydrogen desorption properties of the MgH2 nanoparticles are studied by thermo-desorption spectroscopy. The particle size distribution of MgH2, as determined by TEM, is crucial for understanding the desorption properties. The desorption kinetics are significantly improved by downsizing the particle size below 10 nm. Isothermal absorption/desorption cycling of the MgH2 nanoparticles shows a stable capacity over 13 cycles. The absorption kinetics are unchanged though the desorption kinetics are slower on cycling.

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.

Diverse Nrf2 Activators Coordinated to Cobalt Carbonyls Induce Heme Oxygenase-1 and Release Carbon Monoxide in Vitro and in Vivo

The Nrf2/heme oxygenase-1 (HO-1) axis affords significant protection against oxidative stress and cellular damage. We synthesized a series of cobalt-based hybrid molecules (HYCOs) that combine an Nrf2 inducer with a releaser of carbon monoxide (CO), an anti-inflammatory product of HO-1. Two HYCOs markedly increased Nrf2/HO-1 expression, liberated CO and exerted anti-inflammatory activity in vitro. HYCOs also up-regulated tissue HO-1 and delivered CO in blood after administration in vivo, supporting their potential use against inflammatory conditions.

Anodic Oxidation of Ifosfamide and Cyclophosphamide: A Biomimetic Metabolism Model of the Oxazaphosphorinane Anticancer Drugs

The electrochemical oxidation of anticancer drugs ifosfamide and cyclophosphamide produced in high yield methoxylated analogues of the key hydroxy-metabolites of these oxazaphosphorine prodrugs. The cytotoxicity of these compounds was evaluated, and found to be as high as the hydroxy-metabolite.

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.

Synthesis and cytotoxic evaluation of novel paraconic acid analogs

A novel class of 2,3-tri- and tetrasubstituted γ-butyrolactones analogous to paraconic acids has been synthesized in one step using a straightforward three-component reaction among aryl bromides, dimethyl itaconate and carbonyl compounds. The in vitro cytotoxic activity of representative compounds has been evaluated against a panel of human cancer cell lines (KB, HCT116, MCF7, HL60). While most molecules exhibit a low to moderate background activity on both KB and HL60 cancer cell lines, one compound shows increased antiproliferative activities against both cell lines with IC(50) values in the 10(-7)-10(-6)mol/L range. An extended evaluation indicated that this compound also inhibits PC3, SK-OV3, MCF7R and HL60R cell growth in the same fashion.

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.