Synthetic Cathinones: Recent Developments, Enantioselectivity Studies and Enantioseparation Methods

Abstract

New psychoactive substances represent a public health threat since they are not controlled by international conventions, are easily accessible online and are sold as a legal alternative to illicit drugs. Among them, synthetic cathinones are widely abused due to their stimulant and hallucinogenic effects. To circumvent the law, new derivatives are clandestinely synthesized and, therefore, synthetic cathinones keep emerging on the drug market, with their chemical and toxicological properties still unknown. In this review, a literature assessment about synthetic cathinones is presented focusing on the recent developments, which include more than 50 derivatives since 2014. A summary of their toxicokinetic and toxicodynamic properties are also presented. Furthermore, synthetic cathinones are chiral compounds, meaning that they can exist as two enantiomeric forms which may present different biological and toxicological activities. To analyze the enantiomers, the development of enantiomeric resolution methods for synthetic cathinones is crucial. Many methods have been reported over the years that include mostly chromatographic and electromigration techniques, with liquid chromatography using chiral stationary phases being the technique of choice. This review intended to present an overview of enantioselectivity studies and enantioseparation analysis regarding synthetic cathinones, highlighting the relevance of chirality and current trends.

Synthesis and absolute configuration of cyclic synthetic cathinones derived from α‐tetralone

“…1 H, 13 C, 19 F NMR spectra, and all 2D experiments were carried out using Varian Gemini 400 Hz DDR2 and JEOL-ECZL400G with deuterated solvents (chloroform and methanol). Every sample was measured at 25 C. Deuterated solvents were purchased from Chemstar (Plze ň, Czech Republic).…”

“…During intoxication, a wide range of adverse side effects has been observed, ranging from cardiovascular and neurological to psychiatric effects, such as arterial hypertension, tachycardia, hallucinations, agitation, hyperthermia, and changes in locomotor behavior 9–12 . Due to the chiral center in their structure, cathinones can occur in two enantiomers, with one enantiomer typically exhibiting a greater psychological effect on the human biological system than the other 13,14 . For instance, studies demonstrated that ( S )‐methcathinone possesses a stronger stimulation effect than ( R )‐methcathinone 15 .…”

“…[9][10][11][12] Due to the chiral center in their structure, cathinones can occur in two enantiomers, with one enantiomer typically exhibiting a greater psychological effect on the human biological system than the other. 13,14 For instance, studies demonstrated that (S)methcathinone possesses a stronger stimulation effect than (R)-methcathinone. 15 This fact could be important for the development of new pharmaceuticals based on the cathinone structure, as some synthetic modification can be sought to suppress psychoactivity and enhance pharmaceutical activity.…”

Exploring a Lux® i‐Amylose‐3 column in normal phase and polar‐organic mode for chiral separation of cathinone derivatives and pyrovalerones using high‐performance liquid chromatography

“…For meanwhile established illicit drugs such as mephedrone, and also some newer cathinone derivatives, several studies have been conducted in this regard. 6,7 For mephedrone, it was shown that the enantiomers differ substantially in their neuropharmacological profiles. While for the S-enantiomer higher serotonergic effects were shown, the R-enantiomer displays a much higher preference for the dopaminergic system.…”

“…Furthermore, chiral methods can also be beneficial in semipreparative scale to collect pure enantiomers for further studies, as is already shown in literature for various synthetic cathinones. 7,10,[14][15][16][17] To date, a wide range of different methods for enantioseparation of synthetic cathinones and other NPS exists in gas chromatography (GC), [18][19][20][21] capillary electrophoresis (CE), [21][22][23][24] supercritical fluid chromatography (SFC), 25,26 and high-performance liquid chromatography (HPLC). 6,7,10,19,20,[26][27][28][29][30][31][32] During the last years, various chiral stationary phases (CSPs) have been tested by our working group on the basis of different substance classes of NPS, bought in internet head shops or seized by Austrian Police.…”