Environmentally Friendly Expeditious One-Pot Electrochemical Synthesis of Bis-Catechol-Thioether Metabolites of Ecstasy: in vitro Neurotoxic Effects in the Rat Hippocampus

Abstract

A straightforward one-pot electrochemical synthesis of bis-catechol-thioether metabolites of MDMA (ecstasy), 2,5-bis(glutathion-S-yl)-N-methyl-a-methyldopamine and 2,5-bis(N-acetylcystein-S-yl)-N-methyl-a-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-a-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 discussed through their ability to elicit necrosis and apoptosis on rat hippocampal pyramidal neurons.

Keywords

• anodic oxidation
• ecstasy
• in vitro neurotoxicity
• quinone
• thioether metabolites