Jacques Poupaert

CoA esters of valproic acid and related metabolites are oxidized in peroxisomes through a pathway distinct from peroxisomal fatty and bile acyl-CoA β-oxidation

In rat liver homogenates fortified with the appropriate cofactors (ATP and CoA), valproic acid induced H2O2 production rates by far lower than those recorded on the straight medium‐chain fatty acid n‐octanoic acid. Using directly the CoA esters of these carboxylic acids as substrates for the rat liver H2O2‐generating enzyme activities, valproyl‐CoA, and n‐octanoyl‐CoA were found to induce similar oxidation rates. In the rat liver homogenates, cyanide‐insensitive valproyl‐CoA and octanoyl‐CoA oxidations occurred at rates similar to those of valproyl‐CoA and octanoyl‐CoA oxidase(s), respectively. Studies on fractions obtained from rat liver postnuclear supernatants by isopycnic centrifugation on a linear sucrose density gradient disclose that the density distribution of valproyl‐CoA oxidase superimposes to those of catalase, fatty acyl‐CoA oxidase and cyanide‐insensitive fatty acyl‐CoA oxidation, three peroxisomal marker activities. By contrast, the cyanide‐insensitive valproyl‐CoA oxidation does not adopt the typical peroxisomal distribution of these activities but rather exhibits a mitochondrial localization with, however, a minor peroxisomal component. Interestingly enough, the comparative study of rat tissue distribution, inducibility by clofibrate and sensitivity to deoxycholate indicated that valproyl‐CoA oxidase is an enzyme distinct from fatty acyl‐CoA oxidase and bile acyl‐CoA oxidase. Taken as a whole, the results presented here support the occurrence of a peroxisomal oxidation of the CoA ester of valproic acid and its Δ4‐enoic derivate which might be characterized by two major features: initiation by an acyl‐CoA oxidase distinct from fatty and bile acyl‐CoA oxidases, and inability to complete the β‐oxidation cycle which would not proceed, at significant rates, further than the β‐hydroxyacyl‐CoA dehydrogenation step in peroxisomes.

Willgerodt-Kindler ReactionâÂÂs Microwave-Enhanced Synthesis ofThiobenzamides Derivatives in Heterogeneous Acid Catalysis withMontmorillonite K-10

The Willgerodt-Kindler (WK) reaction of is one of most synthesis methods used to access the thioamides. The known to thioamides have made this reaction more attractive in catalytic synthesis methods. Heterogeneous catalysis acid with the montmorillonite K-10 applied to this reaction under activation microwave for the synthesis of phenyl (morpholino) methanethiones derivatives shows that the mixture (aldehyde, sulfur, morpholine and K-10) is not only appropriate, but optimizes the reaction. This solid catalyst was easily separated from the reaction mixture and was recycled at least twice (02) without any loss of activity. Operational simplicity, short reaction times, excellent yields and benign environmental conditions are other advantages of this protocol, thus respecting the principles of green chemistry. Among the thioamides synthesized, 4-(morpholine-4-carbonothioyl)benzoic acid (h) is a novel molecule which to our knowledge has never before been synthesized. We obtained it with a yield of 68%. In summary, we can be concluded that the heterogeneous catalysis acid conditions with the montmorillonite K - 10 favourable to the Willgerodt-Kindler reaction for carbonyl compounds. The structures of thioamides synthesized were characterized and confirmed by highresolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) 1D and 2D (COSY, HSQC, HMBC).