The Chemistry of Kratom [Mitragyna speciosa]: Updated Characterization Data and Methods to Elucidate Indole and Oxindole Alkaloids

• Published in: Journal of natural products (Washington, D.C.) Vol. 83; no. 7; pp. 2165 - 2177
• Main Authors: Flores-Bocanegra, Laura, Raja, Huzefa A, Graf, Tyler N, Augustinović, Mario, Wallace, E. Diane, Hematian, Shabnam, Kellogg, Joshua J, Todd, Daniel A, Cech, Nadja B, Oberlies, Nicholas H
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society and American Society of Pharmacognosy 24-07-2020
• Subjects: Indole Alkaloids - chemistry; Mitragyna - chemistry; Molecular Structure; Spectrum Analysis - methods; Stereoisomerism
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.0c00257

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 1H and 13C 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 1H and/or 13C NMR spectra.