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

Abstract

<p class="first" id="P1">Two separate commercial products of kratom [ <i>Mitragyna speciosa</i> (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 <b>1</b>- <b>19</b>. Of these, four new alkaloids ( <b>7</b>, <b>11</b>, <b>17</b>, and <b>18</b>) were characterized using 2D NMR data, and the absolute configurations of <b>7</b>, <b>17</b>, and <b>18</b> were established by comparison of experimental and calculated ECD spectra. The absolute configuration for the <i>N</i>(4)-oxide ( <b>11</b>) was established by comparison of NMR and ECD spectra of its reduced product with those for compound <b>7</b>. In total, 19 alkaloids were characterized, including: the indole alkaloid mitragynine ( <b>1</b>) and its diastereoisomers speciociliatine ( <b>2</b>), speciogynine ( <b>3</b>) and mitraciliatine ( <b>4</b>); the indole alkaloid paynantheine ( <b>5</b>) and its diastereoisomers isopaynantheine ( <b>6</b>) and epiallo-isopaynantheine ( <b>7</b>); the <i>N</i>(4)-oxides mitragynine- <i>N</i>(4)-oxide ( <b>8</b>), speciociliatine- <i>N</i>(4)-oxide ( <b>9</b>), isopaynantheine- <i>N</i>(4)-oxide ( <b>10</b>), and epiallo-isopaynantheine- <i>N</i>(4)-oxide ( <b>11</b>); the 9-hydroxylated oxindole alkaloids speciofoline ( <b>12</b>), isorotundifoleine ( <b>13</b>) and isospeciofoleine ( <b>14</b>); and the 9-unsubstituted oxindoles corynoxine A ( <b>15</b>), corynoxine B ( <b>16</b>), 3-epirhynchophylline ( <b>17</b>), 3-epicorynoxine B ( <b>18</b>), and corynoxeine ( <b>19</b>). 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. </p><p id="P2"> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/4f76f62e-b6d8-42e5-95a5-a1870098c68b/PubMedCentral/image/nihms-1647844-f0001.jpg"/> </div> </p>