UR‐144 in products sold via the Internet: Identification of related compounds and characterization of pyrolysis products

Abstract

The synthetic cannabinoid, UR-144 ((1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone), was identified in commercial 'legal high' products (herbal, resin, and powder). Along with this, six related compounds were detected. The most abundant one (2.1) was identified as 4-hydroxy-3,3,4-trimethyl-1-(1-pentyl-1H-indol-3-yl)pentan-1-one, a product of the electrophilic addition of water to the cyclopropane moiety in UR-144. Compound 2.1 was found to be undergo cyclisation which leads to the formation of two additional interconvertable compounds (2.3, tentatively identified as 1-pentyl-3-(4,4,5,5-tetramethyl-4,5-dihydrofuran-2-yl)-1H-indole which is stable only in absence of water and also observed as GC artifact) and 2.2, a protonated derivative of 2.3 which is formed in acidic solutions. The remaining compounds were identified as possible degradation products of the group 2 compounds (4,4,5,5-tetramethyldihydrofuran-2(3H)-one and 1-pentylindoline-2,3-dione) and intermediates or by-products from the synthesis of UR-144 ((1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone, 1-pentyl-1H-indole and 1-(1-pentyl-1H-indol-3-yl)hexan-1-one). Pyrolysis of herbal products containing the group 2 compounds or UR-144 resulted in the formation of 3,3,4-trimethyl-1-(1-pentyl-1H-indol-3-yl)pent-4-en-1-one (3). This was confirmed by separate pyrolysis of 2.1 and UR-144. Also, the two additional minor compounds, 1-(1-pentyl-1H-indol-3-yl)ethanone and 1-(1-pentyl-1H-indol-3-yl)propan-1-one, were detected. Pathways for these transformations are presented.

Pyrolysis of UR-144, a synthetic cannabinoid, augments an affinity to human CB₁ receptor and cannabimimetic effects in mice

“…UR-144 pyrolyzed almost completely into a single component under these conditions. NMR analysis indicated that the obtained compound was identical to a UR-144 degradant in which the cyclopropyl ring was opened, as reported previously ( Kavanagh et al, 2013) (Table 1). Therefore, the pyrolyzed UR-144 was used in the following experiments as the UR-144 degradant.…”

First Metabolic Profile of XLR-11, a Novel Synthetic Cannabinoid, Obtained by Using Human Hepatocytes and High-Resolution Mass Spectrometry

“…Second, the cyclopropyl ring is under strain and has been shown to be unstable under certain conditions. Shevyrin et al (18) and Kavanagh et al (24) proposed ring opening during 2,2,3,3-TMCP cannabinoid stability studies. The cyclopropyl ring can be cleaved when heated, forming isomers carrying a pent-4-en-1-one chain.…”

Genotoxic properties of representatives of alkylindazoles and aminoalkyl-indoles which are consumed as synthetic cannabinoids

“…This compound caused positive effects in single cell gel electrophoresis assays (SCGE) with human derived cells (Koller et al, 2013). UR-144 was detected in many European countries, Japan and in the US (Choi et al, 2013) (Kavanagh et al, 2013;Uchiyama et al, 2013). Furthermore, we investigated in the present study two alkylindazoles.…”