Indazole-derived synthetic cannabinoids: Absolute configuration determination and structure characterization by circular dichroism and DFT calculations

Penn, 2011, Detection of synthetic cannabinoids in herbal incense products, Clin. Biochem., 44, 1163, 10.1016/j.clinbiochem.2011.06.078 Logan, 2012, Identification of Synthetic Cannabinoids in Herbal Incense Blends in the United States, J. Forensic Sci., 57, 1168, 10.1111/j.1556-4029.2012.02207.x European Monitoring Centre for Drugs and Drug Addiction. (2020) European Drug Report 2020: Trends and Developments. https://op.europa.eu/en/publication-detail/-/publication/a3dd1033-fd56-11ea-b44f-01aa75ed71a1/language-en/ (accessed July 20, 2022). European Monitoring Centre for Drugs and Drug Addiction. (2021) European Drug Report 2021: Trends and Developments. https://op.europa.eu/en/publication-detail/-/publication/a9351abd-ce4f-11eb-ac72-01aa75ed71a1/language-en/ (accessed July 20, 2022). Adamowicz, 2019, Fatal intoxication with new synthetic cannabinoids AMB-FUBINACA and EMB-FUBINACA, Clin. Toxicol., 57, 1103, 10.1080/15563650.2019.1580371 Adams, 2017, “Zombie” outbreak caused by the synthetic cannabinoid AMB-FUBINACA in New York, N. Engl. J. Med., 376, 235, 10.1056/NEJMoa1610300 Lam, 2017, Supraventricular tachycardia and acute confusion following ingestion of e-cigarette fluid containing AB-FUBINACA and ADB-FUBINACA: a case report with quantitative analysis of serum drug concentrations, Clin. Toxicol. (Philadelphia Pa.), 55, 662, 10.1080/15563650.2017.1307385 Shanks, 2016, Death Associated With the Use of the Synthetic Cannabinoid ADB-FUBINACA, J. Anal. Toxicol., 40, 236, 10.1093/jat/bkv142 Le Boisselier, 2017, Focus on cannabinoids and synthetic cannabinoids, Clin. Pharmacol. Ther., 101, 220, 10.1002/cpt.563 Howlett, 2017, CB1 and CB2 Receptor Pharmacology, Adv. Pharm. Pharm. Sci., 80, 169, 10.1016/bs.apha.2017.03.007 WHO. Critical Review Report: FUB-AMB (MMB-FUBINACA, AMB-FUBINACA). World Health Organ Technical Report Series 2018. https://www.who.int/medicines/access/controlled-substances/Fub_amb.pdf (accessed September 22, 2020). Banister, 2016, Pharmacology of Valinate and tert-Leucinate Synthetic Cannabinoids 5F-AMBICA, 5F-AMB, 5F-ADB, AMB-FUBINACA, MDMB-FUBINACA, MDMB-CHMICA, and Their Analogues, ACS Chem. Nerosci., 7, 1241, 10.1021/acschemneuro.6b00137 Morrow, 2020, An outbreak of deaths associated with AMB-FUBINACA in Auckland NZ, EClinicalMedicine, 24 I.P. Buchler, M.J. Hayes, S.G. Hegde, S.L. Hockerman, D.E. Jones, S.W. Kortum, et al., Indazole derivatives as CB1 receptor modulators unflagging work flagging work or and their preparation and use in the treatment of CB1-mediated diseases. Patent: WO/2009/106982, 2009. Uchiyama, 2013, Forensic Toxicol., 31, 223, 10.1007/s11419-013-0182-9 Carlier, 2017, In vitro metabolite profiling of ADB-FUBINACA, a new synthetic cannabinoid, Curr. Neuropharmacol., 15, 682, 10.2174/1570159X15666161108123419 Antonides, 2019, Enantiospecific Synthesis, Chiral Separation, and Biological Activity of Four Indazole-3-Carboxamide-Type Synthetic Cannabinoid Receptor Agonists and Their Detection in Seized Drug Samples, Front. Chem., 16, 321, 10.3389/fchem.2019.00321 Banister, 2015, Pharmacology of Indole and Indazole Synthetic Cannabinoid Designer Drugs AB-FUBINACA, ADB-FUBINACA, AB-PINACA, ADB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, ADBICA, and 5F-ADBICA, ACS Chem. Neurosci., 6, 1546, 10.1021/acschemneuro.5b00112 Finlay, 2019, Do Toxic Synthetic Cannabinoid Receptor Agonists Have Signature in Vitro Activity Profiles? A Case Study of AMB-FUBINACA, ACS Chem. Neurosci., 10, 4350, 10.1021/acschemneuro.9b00429 Fabregat-Safont, 2019, Comprehensive investigation on synthetic cannabinoids: Metabolic behavior and potency testing, using 5F-APP-PICA and AMB-FUBINACA as model compounds, Drug Test Anal., 11, 1358, 10.1002/dta.2659 Gatch, 2019, Cannabinoid-like effects of five novel carboxamide synthetic cannabinoids, Neurotoxicology, 70, 72, 10.1016/j.neuro.2018.11.004 Doi, 2018, Evaluation of carboxamide-type synthetic cannabinoids as CB1/CB2 receptor agonists: difference between the enantiomers, Forensic Toxicol., 36, 51, 10.1007/s11419-017-0378-5 Xu, 2019, Analysis of AMB-FUBINACA Biotransformation Pathways in Human Liver Microsome and Zebrafish Systems by Liquid Chromatography-High Resolution Mass Spectrometry, Front. Chem., 7, 240, 10.3389/fchem.2019.00240 Kevin, 2019, Toxic by design? Formation of thermal degradants and cyanide from carboxamide-type synthetic cannabinoids CUMYL-PICA, 5F-CUMYL-PICA, AMB-FUBINACA, MDMB-FUBINACA, NNEI, and MN-18 during exposure to high temperatures, Forensic Toxicol., 37, 17, 10.1007/s11419-018-0430-0 Hamilton, 2017, Synthetic Cannabinoid Abuse Resulting in ST-Segment Elevation Myocardial Infarction Requiring Percutaneous Coronary Intervention, J. Emerg. Med., 52, 496, 10.1016/j.jemermed.2016.09.023 Savchuk, 2017, In vivo metabolism of the new synthetic cannabinoid APINAC in rats by GC–MS and LC–QTOF-MS, Forensic Toxicol., 35, 359, 10.1007/s11419-017-0364-y Al-Matrouk, 2019, Identification of synthetic cannabinoids that were seized, consumed, or associated with deaths in Kuwait in 2018 using GC–MS and LC–MS-MS analysis, Forensic Sci. Int., 303, 10.1016/j.forsciint.2019.109960 Muhamadali, 2019, Rapid Detection and Quantification of Novel Psychoactive Substances (NPS) Using Raman Spectroscopy and Surface-Enhanced Raman Scattering, Front. Chem., 7, 412, 10.3389/fchem.2019.00412 Omar, 2018, Identification of new psychoactive substances (NPS) by Raman spectroscopy, Forensic Sci. Int., 273, 113 Metternich, 2020, Discrimination of synthetic cannabinoids in herbal matrices and of cathinone derivatives by portable and laboratory-based Raman spectroscopy, Forensic Chem., 19, 10.1016/j.forc.2020.100241 de la Asunción-Nadal, 2017, Identification and determination of synthetic cannabinoids in herbal products by dry film attenuated total reflectance-infrared spectroscopy, Talanta, 167, 344, 10.1016/j.talanta.2017.02.026 Qian, 2017, Identification and analytical characterization of four synthetic cannabinoids ADB-BICA, NNL-1, NNL-2, and PPA(N)-2201, Drug Test. Anal., 9, 51, 10.1002/dta.1990 Ernst, 2019, Identification and quantification of synthetic cannabinoids in ‘spice-like’ herbal mixtures: Update of the German situation in summer 2018, Forensic Sci. Int., 294, 96, 10.1016/j.forsciint.2018.11.001 Longworth, 2016, The 2-alkyl-2H-indazole regioisomers of synthetic cannabinoids AB-CHMINACA, AB-FUBINACA, AB-PINACA, and 5F-AB-PINACA are possible manufacturing impurities with cannabimimetic activities, Forensic Toxicol., 34, 286, 10.1007/s11419-016-0316-y Spálovská, 2019, Methylone and pentylone: structural analysis of new psychoactive substances, Forensic Toxicol., 37, 366, 10.1007/s11419-019-00468-z Spálovská, 2021, Structural spectroscopic study of enantiomerically pure synthetic cathinones and their major metabolites, New J. Chem., 45, 850, 10.1039/D0NJ05065B Spálovská, 2018, Structure determination of butylone as a new psychoactive substance using chiroptical and vibrational spectroscopies, Chirality, 30, 548, 10.1002/chir.22825 Fagan, 2017, Cocaine hydrochloride structure in solution revealed by three chiroptical methods, ChemPhysChem, 18, 2258, 10.1002/cphc.201700452 Fowler, 2015, Rapid screening and quantification of synthetic cannabinoids in herbal products with NMR spectroscopic methods, Anal. Methods, 7, 7907, 10.1039/C5AY01754H Castaing-Cordier, 2021, High-field and benchtop NMR spectroscopy for the characterization of new psychoactive substances, Forensic Sci. Int., 321, 10.1016/j.forsciint.2021.110718 Dybowski, 2021, Comprehensive analytical and structural characteristics of methyl 3,3-dimethyl-2-(1-(pent-4-en-1-yl)-1H-indazole-3-carboxamido)butanoate (MDMB-4en-PINACA), Forensic Toxicol., 39, 481, 10.1007/s11419-021-00573-y Abdulsalami, 2018, Comparative Analysis of Theoretical and Empirical Data of Synthetic Cannabinoids, FUJNAS, 7 Polavarapu, 2014, Comparison of experimental and calculated chiroptical spectra for chiral molecular structure determination, Chirality, 26, 539, 10.1002/chir.22316 2012 Jurásek, 2018, Synthesis, absolute configuration and in vitro cytotoxicity of deschloroketamine enantiomers: rediscovered and abused dissociative anaesthetic, New J. Chem., 42, 19360, 10.1039/C8NJ03107J Andernach, 2016, Absolute configuration of the synthetic cannabinoid MDMB-CHMICA with its chemical characteristics in illegal products, Forensic Toxicol., 34, 344, 10.1007/s11419-016-0321-1 Weber, 2016, Characterization of the synthetic cannabinoid MDMB-CHMCZCA, Beilstein J. Org. Chem., 12, 2808, 10.3762/bjoc.12.279 Urbanová, 2000, Measurements of concentration dependence and enantiomeric purity of terpene solutions as a test of a new commercial VCD spectrometer, Chirality, 12, 199, 10.1002/(SICI)1520-636X(2000)12:4<199::AID-CHIR6>3.0.CO;2-L Grimme, 2019, Exploration of Chemical Compound, Conformer, and Reaction Space with Meta-Dynamics Simulations Based on Tight-Binding Quantum Chemical Calculations, J. Chem. Theory Comput., 15, 2847, 10.1021/acs.jctc.9b00143 Frisch, 2016 Xie, 2020, Discovering the Elusive Global Minimum in a Ternary Chiral Cluster: Rotational Spectra of Propylene Oxide Trimer, Angew. Chem. Int. Ed., 59, 22427, 10.1002/anie.202010055 Wang, 2022, Vibrational Spectroscopy of Homo- and Heterochiral Amino Acid Dimers: Conformational Landscapes, Molecules, 27, 38, 10.3390/molecules27010038 Salthammer, 2021, Quantum Chemical Calculation and Evaluation of Partition Coefficients for Classical and Emerging Environmentally Relevant Organic Compounds, Environ. Sci. Tech., 56, 379, 10.1021/acs.est.1c06935