The number of new psychoactive substances (NPS) that have emerged on the European market has been rapidly growing in recent years, with a particularly high number of new compounds from the group of synthetic cannabinoid receptor agonists. There have been various political efforts to control the trade and the use of NPS worldwide. In Germany, the Act to control the distribution of new psychoactive substances (NpSG) came into force in November 2016. In this new act, two groups of substances were defined, the group "cannabimimetics/synthetic cannabinoids" covering indole, indazole, and benzimidazole core structures, and a second group named "compounds derived from 2-phenethylamine." Shortly after, the first retailers of "herbal blends" promoted new products allegedly not violating the German NpSG. We describe the identification and structural elucidation of one of the first synthetic cannabinoids not being covered by the NpSG, 5-pentyl-2-(2-phenylpropan-2-yl)-2,5-dihydro-1H-pyrido[4,3-b]indol-1-one. For isolation of the substance a flash chromatography separation was applied. The structure elucidation was performed using gas chromatography-mass spectrometry (GC-MS), gas chromatography-solid state infrared spectroscopy (GC-sIR), liquid chromatography-electrospray ionization-quadrupole time of flight-mass spectrometry (LC-ESI-qToF-MS) and nuclear magnetic resonance (NMR) analysis. Additionally, binding affinity towards the cannabinoid receptors CB and CB and efficacy in a cAMP accumulation assay were measured, showing full agonistic activity and high potency at both receptors. The new compound bears a γ-carboline core structure circumventing the German NpSG and the generic definitions in other national laws. As a semi-systematic name for 2-cumyl-5-pentyl-gamma-carbolin-1-one CUMYL-PEGACLONE is suggested.

Thiamine diphosphate (ThDP) dependent enzymes are useful catalysts for asymmetric CÀ C bond formation through benzoin-type condensation reactions that result in α-hydroxy ketones. A wide range of aldehydes and ketones can be used as acceptor substrates; however, the donor substrate range is mostly limited to achiral α-keto acids and simple aldehydes. By using a unifying retro-biosynthetic approach towards acyl-branched sugars, we identified a subclass of (myco)bacterial ThDP-dependent enzymes with a greatly extended donor substrate range, namely functionalized chiral α-keto acids with a chain length from C 4 to C 8 . Highly enantioenriched acyloin products were obtained in good to high yields and several reactions were performed on a preparative scale. The newly introduced functionalized αketo acids, accessible by known aldolase-catalyzed transformations, substantially broaden the donor substrate range of ThDP-dependent enzymes, thus enabling a more general use of these already valuable catalysts.

Thiamine diphosphate (ThDP) dependent enzymes are useful catalysts for asymmetric C−C bond formation through benzoin‐type condensation reactions that result in α‐hydroxy ketones. A wide range of aldehydes and ketones can be used as acceptor substrates; however, the donor substrate range is mostly limited to achiral α‐keto acids and simple aldehydes. By using a unifying retro‐biosynthetic approach towards acyl‐branched sugars, we identified a subclass of (myco)bacterial ThDP‐dependent enzymes with a greatly extended donor substrate range, namely functionalized chiral α‐keto acids with a chain length from C4 to C8. Highly enantioenriched acyloin products were obtained in good to high yields and several reactions were performed on a preparative scale. The newly introduced functionalized α‐keto acids, accessible by known aldolase‐catalyzed transformations, substantially broaden the donor substrate range of ThDP‐dependent enzymes, thus enabling a more general use of these already valuable catalysts.