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

Two separate commercial products of kratom [ (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 H and C NMR spectra, along with HRESIMS and ECD data, are reported for alkaloids -. Of these, four new alkaloids (, , , and ) were characterized using 2D NMR data, and the absolute configurations of , , and were established by comparison of experimental and calculated ECD spectra. The absolute configuration for the (4)-oxide () was established by comparison of NMR and ECD spectra of its reduced product with those for compound . In total, 19 alkaloids were characterized, including the indole alkaloid mitragynine () and its diastereoisomers speciociliatine (), speciogynine (), and mitraciliatine (); the indole alkaloid paynantheine () and its diastereoisomers isopaynantheine () and epiallo-isopaynantheine (); the (4)-oxides mitragynine-(4)-oxide (), speciociliatine-(4)-oxide (), isopaynantheine-(4)-oxide (), and epiallo-isopaynantheine-(4)-oxide (); the 9-hydroxylated oxindole alkaloids speciofoline (), isorotundifoleine (), and isospeciofoleine (); and the 9-unsubstituted oxindoles corynoxine A (), corynoxine B (), 3-epirhynchophylline (), 3-epicorynoxine B (), and corynoxeine (). 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 H and/or C NMR spectra.