Studies in the synthesis and impurity profiling of Methylenedioxy and Alkylthioamphetamines

Abstract

3,4-Methylenedioxymethamphetamme (MDMA, Ecstasy) and other, so-called, designer amphetamines, have become popular drugs of abuse over the past number of years. Detailed knowledge of the synthetic methods employed by clandestine chemists towards their manufacture provides valuable information to drug enforcement agencies and may assist in the detection and seizure of illegal underground laboratories. Further knowledge of the impurities that are formed as by-products of illicit amphetamine manufacture enhances the ability of determining the synthetic route employed. The ability to identify impurities which arise from one particular route and no other (so-called route specific impurties), are of particular interest to the forensic chemist. Many amphetamines, including MDMA, its butanamine analogue 2-N-methylamino-1-(3,4- methylenedioxyphenyl)butane (MBDB) and 4-methylthioamphetamine (4-MTA), exert their pharmacological effects in humans by increasing extracellular serotonin concentrations in the brain. This is mediated primarily by their ability to inhibit the transmembrane serotonin transporter (SERT) protein, which is expressed on presynaptic serotonergic nerve terminals. A number of drugs, which are highly selective serotonin reuptake inhibitors (SSRI’s), are clinically used in the treatment of depression. Chemical modification of MDMA, MBDB and 4-MTA may result in SERT inhibitors which possess increased selectivity and potency and may ultimately lead to new drug candidates with potential antidepressant properties.