Synthesis and absolute configuration of cyclic synthetic cathinones derived from α-tetralone
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články
Grantová podpora
Vysoká Škola Chemicko-technologická v Praze
21-31139J
Czech Science Foundation
VK01010212
Ministry of the Interior of the Czech Republic
A2_FCHI_2023_025
Specific University Research
A2_FCHT_2023_063
Specific University Research
A1_FCHT_2023_006
Specific University Research
PubMed
38353318
DOI
10.1002/chir.23646
Knihovny.cz E-zdroje
- Klíčová slova
- 2-amino-α-tetralone synthesis, chiral separation, circular dichroism, determination of absolute configuration, new psychoactive substances, on-line circular dichroism spectra, synthetic cathinones,
- MeSH
- cirkulární dichroismus MeSH
- stereoizomerie MeSH
- syntetický kathinon * MeSH
- tetralony * MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- syntetický kathinon * MeSH
- tetralony * MeSH
The emergence of new synthetic cathinones continues to be a matter of public health concern. In fact, already known products (drugs) are being rapidly replaced by new structurally related alternatives, whereby modifications in the basic cathinone structure are used by manufacturers to circumvent the legislation. On the other hand, some derivatives of synthetic cathinones represent important pharmaceuticals with antidepressant properties. In the search for pharmaceutically relevant analogs, the main goal of the present study was to design and characterize novel cyclic α-tetralone-based derivatives of synthetic cathinones. We synthesized a series of derivatives and verified their chemical structure. Subsequently, chiral separation has been accomplished by high-performance liquid chromatography (HPLC) equipped with a circular dichroism (CD) detector, which directly provided CD spectra of the enantiomers of the analyzed substances at 252 nm. Using density functional theory calculations, we have obtained stable conformers of selected enantiomers in solution and their relative abundances, which we used to simulate their spectra. The experimental and calculated data have been used to assign the absolute configuration of six as-yet unknown synthetic cathinones.
Department of Analytical Chemistry University of Chemistry and Technology Prague 6 Czech Republic
Department of Organic Chemistry University of Chemistry and Technology Prague 6 Czech Republic
Psychedelic Research Centre National Institute of Mental Health Klecany Czech Republic
Zobrazit více v PubMed
European Monitoring Centre for Drugs and Drug Addiction. European drug report 2022: Trends and developments. Publications Office of the European Union; 2022.
European Monitoring Centre for Drugs and Drug Addiction. European drug report 2021: Trends and developments. Publications Office of the European Union; 2021.
Fass JA, Fass AD, Garcia AS. Synthetic cathinones (bath salts): legal status and patterns of abuse. Ann Pharmacother. 2012;46(3):436-441. doi:10.1345/aph.1Q628
Hassan NAGM, Gunaid AA, Murray Lyon IM. Khat (Catha edulis): health aspects of khat chewing. East Mediterr Health J. 2007;13(3):706-718.
German CL, Fleckenstein AE, Hanson GR. Bath salts and synthetic cathinones: an emerging designer drug phenomenon. Life Sci. 2014;97(1):2-8. doi:10.1016/j.lfs.2013.07.023
Ezaki J, Ro A, Hasegawa M, Kibayashi K. Fatal overdose from synthetic cannabinoids and cathinones in Japan: demographics and autopsy findings. Am J Drug Alcohol Abuse. 2016;42(5):520-529. doi:10.3109/00952990.2016.1172594
James D, Adams RD, Spears R, et al. Clinical characteristics of mephedrone toxicity reported to the U.K. National Poisons Information Service. Emerg Med J. 2011;28(8):686-689. doi:10.1136/emj.2010.096636
La Maida N, Di Trana A, Giorgetti R, Tagliabracci A, Busardò FP, Huestis MA. A review of synthetic cathinone-related fatalities from 2017 to 2020. Ther Drug Monit. 2021;43(1):52-68. doi:10.1097/FTD.0000000000000808
Coppola M, Mondola R. 3, 4-methylenedioxypyrovalerone (MDPV): chemistry, pharmacology and toxicology of a new designer drug of abuse marketed online. Toxicol Lett. 2012;208(1):12-15. doi:10.1016/j.toxlet.2011.10.002
Papaseit E, Moltó J, Muga R, Torrens M, de la Torre R, Farré M. Clinical pharmacology of the synthetic cathinone Mephedrone. Curr Top Behav Neurosci. 2017;32:313-331. doi:10.1007/7854_2016_61
Spiller HA, Ryan ML, Weston RG, Jansen J. Clinical experience with and analytical confirmation of “bath salts” and “legal highs”(synthetic cathinones) in the United States. Clin Toxicol. 2011;49(6):499-505. doi:10.3109/15563650.2011.590812
Weinstein AM, Rosca P, Fattore L, London ED. Synthetic cathinone and cannabinoid designer drugs pose a major risk for public health. Front Psych. 2017;8:156. doi:10.3389/fpsyt.2017.00156
Almeida AS, Silva B, Pinho PG, Remião F, Fernandes C. Synthetic Cathinones: recent developments, Enantioselectivity studies and Enantioseparation methods. Molecules. 2022;27(7):2057. doi:10.3390/molecules27072057
Silva B, Fernandes C, Guedes de Pinho P, Remião F. Chiral resolution and Enantioselectivity of synthetic Cathinones: a brief review. J Anal Toxicol. 2018;42(1):17-24. doi:10.1093/jat/bkx074
Dal Cason TA, Young R, Glennon RA. Cathinone: an investigation of several N-alkyl and methylenedioxy-substituted analogs. Pharmacol Biochem Behav. 1997;58(4):1109-1116. doi:10.1016/S0091-3057(97)00323-7
Flack HD, Bernardinelli G. The use of X-ray crystallography to determine absolute configuration. Chirality. 2008;20(5):681-690. doi:10.1002/chir.20473
Parsons S. Determination of absolute configuration using X-ray diffraction. Tetrahedron. 2017;28(10):1304-1313. doi:10.1016/j.tetasy.2017.08.018
Kerti G, Kurtán T, Illyés T-Z, et al. Enantioselective synthesis of 3-Methylisochromans and determination of their absolute configurations by circular dichroism. Eur J Org Chem. 2007;2007(2):296-305. doi:10.1002/ejoc.200600678
Pescitelli G, Berova N, Xiao TL, Rozhkov RV, Larock RC, Armstrong DW. Assignment of absolute configuration of a chiral phenyl-substituted dihydrofuroangelicin. Org Biomol Chem. 2003;1(1):186-190. doi:10.1039/b207652g
Polavarapu PL. Determination of the absolute configurations of chiral drugs using Chiroptical spectroscopy. Molecules. 2016;21(8):1056. doi:10.3390/molecules21081056
Tichotová M, Landovský T, Lang J, et al. Enantiodiscrimination of inherently chiral Thiacalixarenes by residual dipolar couplings. J Org Chem. 2023. doi:10.1021/acs.joc.2c02594
Wenzel TJ. Strategies for using NMR spectroscopy to determine absolute configuration. Tetrahedron. 2017;28(10):1212-1219. doi:10.1016/j.tetasy.2017.09.009
Favretto D, Pascali JP, Tagliaro F. New challenges and innovation in forensic toxicology: focus on the “new psychoactive substances”. J Chromatogr A. 2013;1287:84-95. doi:10.1016/j.chroma.2012.12.049
Gerace E, Caneparo D, Borio F, Salomone A, Vincenti M. Determination of several synthetic cathinones and an amphetamine-like compound in urine by gas chromatography with mass spectrometry. Method validation and application to real cases. J Sep Sci. 2019;42(8):1577-1584. doi:10.1002/jssc.201801249
Kolderová N, Jurásek B, Kuchař M, Lindner W, Kohout M. Gradient supercritical fluid chromatography coupled to mass spectrometry with a gradient flow of make-up solvent for enantioseparation of cathinones. J Chromatogr A. 2020;1625:461286. doi:10.1016/j.chroma.2020.461286
Bringmann G, Gulder TAM, Reichert M, Gulder T. The online assignment of the absolute configuration of natural products: HPLC-CD in combination with quantum chemical CD calculations. Chirality. 2008;20(5):628-642. doi:10.1002/chir.20557
Kirkpatrick D, Fain M, Yang J, Trehy M. Enantiomeric impurity analysis using circular dichroism spectroscopy with United States Pharmacopeia liquid chromatographic methods. J Pharm Biomed Anal. 2018;156:366-371. doi:10.1016/j.jpba.2018.04.033
Lecoeur-Lorin M, Delépée R, Adamczyk M, Morin P. Simultaneous determination of optical and chemical purities of a drug with two chiral centers by liquid chromatography-circular dichroism detection on a non-chiral stationary phase. J Chromatogr A. 2008;1206(2):123-130. doi:10.1016/j.chroma.2008.08.004
Luykx DM, Goerdayal SS, Dingemanse PJ, Jiskoot W, Jongen PM. HPLC and tandem detection to monitor conformational properties of biopharmaceuticals. J Chromatogr B Analyt Technol Biomed Life Sci. 2005;821(1):45-52. doi:10.1016/j.jchromb.2005.04.005
Sánchez FG, Díaz AN, de Vicente AB. Enantiomeric resolution of bupivacaine by high-performance liquid chromatography and chiroptical detection. J Chromatogr A. 2008;1188(2):314-317. doi:10.1016/j.chroma.2008.02.070
Eto S, Yamaguchi M, Bounoshita M, Mizukoshi T, Miyano H. High-throughput comprehensive analysis of D- and L-amino acids using ultra-high performance liquid chromatography with a circular dichroism (CD) detector and its application to food samples. J Chromatogr B Analyt Technol Biomed Life Sci. 2011;879(29):3317-3325. doi:10.1016/j.jchromb.2011.07.025
Gergely A, Szász G, Szentesi A, et al. Evaluation of CD detection in an HPLC system for analysis of DHEA and related steroids. Anal Bioanal Chem. 2006;384(7-8):1506-1510. doi:10.1007/s00216-006-0318-4
Rebizi MN, Sekkoum K, Petri A, Pescitelli G, Belboukhari N. Synthesis, enantioseparation, and absolute configuration assignment of iminoflavans by chiral high-performance liquid chromatography combined with online chiroptical detection. J Sep Sci. 2021;44(19):3551-3561. doi:10.1002/jssc.202100474
Frisch MJ, Trucks GW, Schlegel HB, et al. Gaussian 16 Rev. C.01. Wallingford, CT; 2016.
Salthammer T, Grimme S, Stahn M, Hohm U, Palm W-U. Technology. Quantum chemical calculation and evaluation of partition coefficients for classical and emerging environmentally relevant organic compounds. Environ Sci Technol. 2021;56(1):379-391. doi:10.1021/acs.est.1c06935
Wang H, Heger M, Al-Jabiri MH, Xu Y. Vibrational spectroscopy of homo- and Heterochiral amino acid dimers: conformational landscapes. Molecules. 2022;27(1):38. doi:10.3390/molecules27010038
Xie F, Fusè M, Hazrah AS, Jäger W, Barone V, Xu Y. Discovering the elusive global minimum in a ternary chiral cluster: rotational spectra of propylene oxide trimer. Angew Chem Int Ed. 2020;59(50):22427-22430. doi:10.1002/anie.202010055
Covington CL, Polavarapu PL. Similarity in dissymmetry factor spectra: a quantitative measure of comparison between experimental and predicted vibrational circular dichroism. J Phys Chem A. 2013;117(16):3377-3386. doi:10.1021/jp401079s
Polavarapu PL, Covington CL. Comparison of experimental and calculated chiroptical spectra for chiral molecular structure determination. Chirality. 2014;26(9):539-552. doi:10.1002/chir.22316
Kohout M, Vandenbussche J, Roller A, et al. Absolute configuration of the antimalarial erythro-mefloquine - vibrational circular dichroism and X-ray diffraction studies of mefloquine and its thiourea derivative. RSC Adv. 2016;6(85):81461-81465. doi:10.1039/C6RA19367F
Kuppens T, Langenaeker W, Tollenaere JP, Bultinck P. Determination of the stereochemistry of 3-Hydroxymethyl-2,3-dihydro-[1,4]dioxino[2,3-b]- pyridine by vibrational circular dichroism and the effect of DFT integration grids. J Phys Chem A. 2003;107(4):542-553. doi:10.1021/jp021822g
Bruhn T, Schaumlöffel A, Hemberger Y, Bringmann G. SpecDis: quantifying the comparison of calculated and experimental electronic circular dichroism spectra. Chirality. 2013;25(4):243-249. doi:10.1002/chir.22138
Dobšíková K, Javorská Ž, Paškan M, et al. Enantioseparation and a comprehensive spectroscopic analysis of novel synthetic cathinones laterally substituted with a trifluoromethyl group. Spectrochim Acta A Mol Biomol Spectrosc. 2023;291:122320. doi:10.1016/j.saa.2023.122320
Paškan M, Rimpelová S, Svobodová Pavlíčková V, et al. 4-Isobutylmethcathinone: a novel synthetic cathinone with high in vitro cytotoxicity and strong receptor binding preference of enantiomers. Pharmaceuticals. 2022;15(12):1495. doi:10.3390/ph15121495
Spálovská D, Maříková T, Kohout M, Králík F, Kuchař M, Setnička V. Methylone and pentylone: structural analysis of new psychoactive substances. Forensic Toxicol. 2019;37(2):366-377. doi:10.1007/s11419-019-00468-z
Spálovská D, Paškan M, Jurásek B, Kuchař M, Kohout M, Setnička V. Structural spectroscopic study of enantiomerically pure synthetic cathinones and their major metabolites. New J Chem. 2021;45(2):850-860. doi:10.1039/D0NJ05065B
Carroll FI, Blough BE, Abraham P, et al. Synthesis and biological evaluation of bupropion analogues as potential pharmacotherapies for cocaine addiction. J Med Chem. 2009;52(21):6768-6781. doi:10.1021/jm901189z