Environmentally friendly expeditious one-pot electrochemical synthesis of bis-catechol-thioether metabolites of ecstasy: in vitro neurotoxic effects in the rat hippocampus

Anne Felim (1) , Anne Neudorffer (1) , François P. Monnet (2) , Martine Largeron (3)

1 SSMIP - Synthèse et structure de molécules d'interet pharmacologique
2 NAVVEC - UM 81 (UMR 8206/ U705) - Neuropsychopharmacologie des addictions. Vulnérabilité et variabilité expérimentale et clinique
3 CiTCoM - UMR 8038 - Cibles Thérapeutiques et conception de médicaments

A straightforward one-pot electrochemical synthesis of bis-catechol-thioether metabolites of MDMA (ecstasy), 2,5-bis(glutathion-S-yl)-N-methyl--methyldopamine and 2,5-bis(N-acetylcystein-S-yl)-N-methyl--methyldopamine, in acceptable yields and high degree of purity (99%), is described under environmentally friendly conditions. The undeniable benefits of this method, which uses N-methyl--methyldopamine as the starting catechol, without the need to isolate the catechol-thioether mono-conjugate intermediate, include atom economy, as well as economies of time, resource management, and waste generation. Finally, the possible participation of the catechol-thioether bis-conjugates in the long-term neurotoxic effects of MDMA is dicussed through their ability to elicit necrosis and apoptosis on rat hippocampal pyramidal neurons.

Mots clés: anodic oxidation; ecstasy; in vitro neurotoxicity; quinone; thioether metabolites.

Domaines: Chimie thérapeutique; Autre; Toxicologie; Neurobiologie

Anne Felim, Anne Neudorffer, François P. Monnet, Martine Largeron. Environmentally friendly expeditious one-pot electrochemical synthesis of bis-catechol-thioether metabolites of ecstasy: in vitro neurotoxic effects in the rat hippocampus. International Journal of Electrochemical Science, 2008, 3 (2), pp.266-281. ⟨hal-03138868⟩