1. The Chemistry of Kratom [Mitragyna speciosa]: Updated Characterization Data and Methods to Elucidate Indole and Oxindole Alkaloids
- Author
-
Mario Augustinović, Nadja B. Cech, Daniel A. Todd, Laura Flores-Bocanegra, Nicholas H. Oberlies, Shabnam Hematian, E. Diane Wallace, Huzefa A. Raja, Joshua J. Kellogg, and Tyler N. Graf
- Subjects
Stereochemistry ,Mitragyna speciosa ,Pharmaceutical Science ,01 natural sciences ,Article ,Indole Alkaloids ,Analytical Chemistry ,chemistry.chemical_compound ,Drug Discovery ,Oxindole ,Pharmacology ,Indole test ,Molecular Structure ,biology ,Indole alkaloid ,Mitragyna ,010405 organic chemistry ,Chemistry ,Spectrum Analysis ,Organic Chemistry ,Absolute configuration ,Stereoisomerism ,Carbon-13 NMR ,biology.organism_classification ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Complementary and alternative medicine ,Mitragynine ,Molecular Medicine ,Two-dimensional nuclear magnetic resonance spectroscopy - Abstract
Two separate commercial products of kratom [Mitragyna speciosa (Korth.) Havil. Rubiaceae] were used to generate reference standards of its indole and oxindole alkaloids. While kratom has been studied for over a century, the characterization data in the literature for many of the alkaloids are either incomplete or inconsistent with modern standards. As such, full (1)H and (13)C NMR spectra, along with HRESIMS and ECD data, are reported for alkaloids 1-19. Of these, four new alkaloids (7, 11, 17, and 18) were characterized using 2D NMR data, and the absolute configurations of 7, 17, and 18 were established by comparison of experimental and calculated ECD spectra. The absolute configuration for the N(4)-oxide (11) was established by comparison of NMR and ECD spectra of its reduced product with those for compound 7. In total, 19 alkaloids were characterized, including: the indole alkaloid mitragynine (1) and its diastereoisomers speciociliatine (2), speciogynine (3) and mitraciliatine (4); the indole alkaloid paynantheine (5) and its diastereoisomers isopaynantheine (6) and epiallo-isopaynantheine (7); the N(4)-oxides mitragynine-N(4)-oxide (8), speciociliatine-N(4)-oxide (9), isopaynantheine-N(4)-oxide (10), and epiallo-isopaynantheine-N(4)-oxide (11); the 9-hydroxylated oxindole alkaloids speciofoline (12), isorotundifoleine (13) and isospeciofoleine (14); and the 9-unsubstituted oxindoles corynoxine A (15), corynoxine B (16), 3-epirhynchophylline (17), 3-epicorynoxine B (18), and corynoxeine (19). With the ability to analyze the spectroscopic data of all of these compounds concomitantly, a decision tree was developed to differentiate these kratom alkaloids based on a few key chemical shifts in the (1)H and/or (13)C NMR spectra.
- Published
- 2020