Prediction of designer drugs: synthesis and spectroscopic analysis of synthetic cannabinoid analogues of 1H‐indol‐3‐yl(2,2,3,3‐tetramethylcyclopropyl)methanone and 1H‐indol‐3‐yl(adamantan‐1‐yl)methanone

Abstract

In this work, emergence patterns of synthetic cannabinoids were utilized in an attempt to predict those that may appear on the drug market in the future. Based on this information, two base structures of the synthetic cannabinoid analogues - (1H-indol-3-yl(2,2,3,3-tetramethylcyclopropyl)methanone and 1H-indol-3-yl(adamantan-1-yl)methanone) - together with three substituents - butyl, 4-fluorobutyl and ethyl tetrahydropyran - were selected for synthesis. This resulted in a total of six synthetic cannabinoid analogues that to the authors' knowledge have not yet appeared on the drug market. Spectroscopic data, including nuclear magnetic resonance (NMR), mass spectrometry (MS), and Fourier transform infrared (FTIR) spectroscopy (solid and gas phase), are presented for the synthesized analogues and some additional related cannabinoids. In this context, the suitability of the employed techniques for the identification of unknowns is discussed and the use of GC-FTIR as a secondary complementary technique to GC-MS is addressed. Examples of compounds that are difficult to differentiate by their mass spectra, but can be distinguished based upon their gas phase FTIR spectra are presented. Conversely, structural homologues where mass spectra are more powerful than gas phase FTIR spectra for unambiguous assignments are also exemplified. This work further emphasizes that a combination of several techniques is the key to success in structural elucidations. Copyright © 2015 John Wiley & Sons, Ltd.

Identification and analytical characterization of six synthetic cannabinoids NNL‐3, 5F–NPB‐22‐7N, 5F–AKB‐48‐7N, 5F–EDMB‐PINACA, EMB‐FUBINACA, and EG‐018

“…[28,29] was an additional CH 2 . Compound 4 had the identical fragment ions of C 8 [28] Therefore, compound 4 was presumed to be a 5F-MDMB-PINACA ethyl analogue.…”

“…Synthetic cannabinoids (SCs) dominate seizures of NPS, and new types of SCs with increasing structural diversity are continually being made. [7][8][9][10][11][12][13][14][15][16][17] As of December 2015, over 644 NPS have been reported by 102 countries to the United Nations Office on Drugs and Crime (UNODC) Early Warning Advisory (EWA); among them SCs accounted for 35%. [4] According to data from the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) Early Warning System, 50 000 seized NPS were reported in 2014 and over 60% of these were SCs.…”

The chemistry and pharmacology of synthetic cannabinoid SDB‐006 and its regioisomeric fluorinated and methoxylated analogs

“…17 Proactive characterization of predicted NPS is essential to the early identification of emergent drugs of abuse. 19,20 The incorporation of fluorine or methoxy substituents in SC analogs has proven a popular clandestine design trend. 19,20 The incorporation of fluorine or methoxy substituents in SC analogs has proven a popular clandestine design trend.…”

“…Toxicologists have utilized non-targeted search methods to identify hitherto unknown SCs, 18 and chemists have used Internet surveillance and chemical intuition to identify novel SCs based on anticipated analogs of prevalent known SCs. 19,20 The incorporation of fluorine or methoxy substituents in SC analogs has proven a popular clandestine design trend. 21,22 Analogs of JWH-018 containing a fluorine substituent (JWH-412, 3) or a methoxy group (JWH-081, 4) on the naphthalene ring have been identified in SC products from the marketplace or authentic SC user specimens.…”

Synthesis and spectroscopic characterization of emerging synthetic cannabinoids and cathinones

“…Efforts aiming at predict possible future NPS have been performed by other research groups. [95][96][97] The synthesis described by Smolianitski et al, focuses on the formation of cyclic ketals and thioketals, and resulted in nine new cathinone derivatives. Kavanagh et al describe the synthesis of isomers of metylenedioxypyrovalerone (MDPV), butylone and methylone.…”