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

Laura Flores-Bocanegra, Huzefa A. Raja, Tyler N. Graf, Mario Augustinović, E. Diane Wallace, Shabnam Hematian, Joshua J. Kellogg, Daniel A. Todd, Nadja B. Cech, Nicholas H. Oberlies

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)2165-2177
Number of pages13
JournalJournal of Natural Products
Volume83
Issue number7
DOIs
StatePublished - Jul 24 2020

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

Fingerprint Dive into the research topics of 'The Chemistry of Kratom [ Mitragyna speciosa]: Updated Characterization Data and Methods to Elucidate Indole and Oxindole Alkaloids'. Together they form a unique fingerprint.

  • Cite this

    Flores-Bocanegra, L., Raja, H. A., Graf, T. N., Augustinović, M., Wallace, E. D., Hematian, S., Kellogg, J. J., Todd, D. A., Cech, N. B., & Oberlies, N. H. (2020). The Chemistry of Kratom [ Mitragyna speciosa]: Updated Characterization Data and Methods to Elucidate Indole and Oxindole Alkaloids. Journal of Natural Products, 83(7), 2165-2177. https://doi.org/10.1021/acs.jnatprod.0c00257