Structurally Diverse Diterpenoids from Sandwithia guyanensis

Bioassay-guided fractionation of an EtOAc extract of the trunk bark of Sandwithia guyanensis, using a chikungunya virus (CHIKV)-cell-based assay, afforded 17 new diterpenoids <b>1</b>–<b>17</b> and the known jatrointelones A and C (<b>18</b> and <b>19</b>). The new compounds included two tetranorditerpenoids <b>1</b> and <b>2</b>, a trinorditerpenoid <b>3</b>, euphoractines P-W (<b>4</b>–<b>11</b>), and euphactine G (<b>13</b>) possessing the rare 5/6/7/3 (<b>4</b>–<b>7</b>), 5/6/6/4 (<b>8</b>–<b>11</b>), and 5/6/8 (<b>13</b>) fused ring skeletons, sikkimenoid E (<b>12</b>), and jatrointelones J-M (<b>14</b>–<b>17</b>) possessing jatropholane and lathyrane carbon skeletons, respectively. Jatrointelones J (<b>14</b>) and M (<b>17</b>) represent the first naturally occurring examples of C-15 nonoxidized lathyrane-type diterpenoids. The structures of the new compounds were elucidated by NMR spectroscopic data analysis. The relative configuration of compound <b>16</b> and the absolute configurations of compounds <b>3</b>–<b>6</b> and <b>14</b> were determined by single-crystal X-ray diffraction analysis. In addition, jatrointelone K (<b>15</b>) was chemically transformed to euphoractine T (<b>8</b>) supporting the biosynthetic relationships between the two types of diterpenoids. Only compound <b>15</b> showed a moderate anti-CHIKV activity with an EC₅₀ value of 14 μM. Finally, using a molecular networking-based dereplication strategy, several close analogues of 12-<i>O</i>-tetradecanoylphorbol-13-acetate (TPA), one of the most potent inhibitors of CHIKV replication, were dereplicated

Structurally Diverse Diterpenoids from Sandwithia guyanensis

Bioassay-guided fractionation of an EtOAc extract of the trunk bark of Sandwithia guyanensis, using a chikungunya virus (CHIKV)-cell-based assay, afforded 17 new diterpenoids <b>1</b>–<b>17</b> and the known jatrointelones A and C (<b>18</b> and <b>19</b>). The new compounds included two tetranorditerpenoids <b>1</b> and <b>2</b>, a trinorditerpenoid <b>3</b>, euphoractines P-W (<b>4</b>–<b>11</b>), and euphactine G (<b>13</b>) possessing the rare 5/6/7/3 (<b>4</b>–<b>7</b>), 5/6/6/4 (<b>8</b>–<b>11</b>), and 5/6/8 (<b>13</b>) fused ring skeletons, sikkimenoid E (<b>12</b>), and jatrointelones J-M (<b>14</b>–<b>17</b>) possessing jatropholane and lathyrane carbon skeletons, respectively. Jatrointelones J (<b>14</b>) and M (<b>17</b>) represent the first naturally occurring examples of C-15 nonoxidized lathyrane-type diterpenoids. The structures of the new compounds were elucidated by NMR spectroscopic data analysis. The relative configuration of compound <b>16</b> and the absolute configurations of compounds <b>3</b>–<b>6</b> and <b>14</b> were determined by single-crystal X-ray diffraction analysis. In addition, jatrointelone K (<b>15</b>) was chemically transformed to euphoractine T (<b>8</b>) supporting the biosynthetic relationships between the two types of diterpenoids. Only compound <b>15</b> showed a moderate anti-CHIKV activity with an EC₅₀ value of 14 μM. Finally, using a molecular networking-based dereplication strategy, several close analogues of 12-<i>O</i>-tetradecanoylphorbol-13-acetate (TPA), one of the most potent inhibitors of CHIKV replication, were dereplicated

Structurally Diverse Diterpenoids from Sandwithia guyanensis

Bioassay-guided fractionation of an EtOAc extract of the trunk bark of Sandwithia guyanensis, using a chikungunya virus (CHIKV)-cell-based assay, afforded 17 new diterpenoids <b>1</b>–<b>17</b> and the known jatrointelones A and C (<b>18</b> and <b>19</b>). The new compounds included two tetranorditerpenoids <b>1</b> and <b>2</b>, a trinorditerpenoid <b>3</b>, euphoractines P-W (<b>4</b>–<b>11</b>), and euphactine G (<b>13</b>) possessing the rare 5/6/7/3 (<b>4</b>–<b>7</b>), 5/6/6/4 (<b>8</b>–<b>11</b>), and 5/6/8 (<b>13</b>) fused ring skeletons, sikkimenoid E (<b>12</b>), and jatrointelones J-M (<b>14</b>–<b>17</b>) possessing jatropholane and lathyrane carbon skeletons, respectively. Jatrointelones J (<b>14</b>) and M (<b>17</b>) represent the first naturally occurring examples of C-15 nonoxidized lathyrane-type diterpenoids. The structures of the new compounds were elucidated by NMR spectroscopic data analysis. The relative configuration of compound <b>16</b> and the absolute configurations of compounds <b>3</b>–<b>6</b> and <b>14</b> were determined by single-crystal X-ray diffraction analysis. In addition, jatrointelone K (<b>15</b>) was chemically transformed to euphoractine T (<b>8</b>) supporting the biosynthetic relationships between the two types of diterpenoids. Only compound <b>15</b> showed a moderate anti-CHIKV activity with an EC₅₀ value of 14 μM. Finally, using a molecular networking-based dereplication strategy, several close analogues of 12-<i>O</i>-tetradecanoylphorbol-13-acetate (TPA), one of the most potent inhibitors of CHIKV replication, were dereplicated

Structurally Diverse Diterpenoids from Sandwithia guyanensis

Bioassay-guided fractionation of an EtOAc extract of the trunk bark of Sandwithia guyanensis, using a chikungunya virus (CHIKV)-cell-based assay, afforded 17 new diterpenoids <b>1</b>–<b>17</b> and the known jatrointelones A and C (<b>18</b> and <b>19</b>). The new compounds included two tetranorditerpenoids <b>1</b> and <b>2</b>, a trinorditerpenoid <b>3</b>, euphoractines P-W (<b>4</b>–<b>11</b>), and euphactine G (<b>13</b>) possessing the rare 5/6/7/3 (<b>4</b>–<b>7</b>), 5/6/6/4 (<b>8</b>–<b>11</b>), and 5/6/8 (<b>13</b>) fused ring skeletons, sikkimenoid E (<b>12</b>), and jatrointelones J-M (<b>14</b>–<b>17</b>) possessing jatropholane and lathyrane carbon skeletons, respectively. Jatrointelones J (<b>14</b>) and M (<b>17</b>) represent the first naturally occurring examples of C-15 nonoxidized lathyrane-type diterpenoids. The structures of the new compounds were elucidated by NMR spectroscopic data analysis. The relative configuration of compound <b>16</b> and the absolute configurations of compounds <b>3</b>–<b>6</b> and <b>14</b> were determined by single-crystal X-ray diffraction analysis. In addition, jatrointelone K (<b>15</b>) was chemically transformed to euphoractine T (<b>8</b>) supporting the biosynthetic relationships between the two types of diterpenoids. Only compound <b>15</b> showed a moderate anti-CHIKV activity with an EC₅₀ value of 14 μM. Finally, using a molecular networking-based dereplication strategy, several close analogues of 12-<i>O</i>-tetradecanoylphorbol-13-acetate (TPA), one of the most potent inhibitors of CHIKV replication, were dereplicated

Structurally Diverse Diterpenoids from Sandwithia guyanensis

Bioassay-guided fractionation of an EtOAc extract of the trunk bark of Sandwithia guyanensis, using a chikungunya virus (CHIKV)-cell-based assay, afforded 17 new diterpenoids <b>1</b>–<b>17</b> and the known jatrointelones A and C (<b>18</b> and <b>19</b>). The new compounds included two tetranorditerpenoids <b>1</b> and <b>2</b>, a trinorditerpenoid <b>3</b>, euphoractines P-W (<b>4</b>–<b>11</b>), and euphactine G (<b>13</b>) possessing the rare 5/6/7/3 (<b>4</b>–<b>7</b>), 5/6/6/4 (<b>8</b>–<b>11</b>), and 5/6/8 (<b>13</b>) fused ring skeletons, sikkimenoid E (<b>12</b>), and jatrointelones J-M (<b>14</b>–<b>17</b>) possessing jatropholane and lathyrane carbon skeletons, respectively. Jatrointelones J (<b>14</b>) and M (<b>17</b>) represent the first naturally occurring examples of C-15 nonoxidized lathyrane-type diterpenoids. The structures of the new compounds were elucidated by NMR spectroscopic data analysis. The relative configuration of compound <b>16</b> and the absolute configurations of compounds <b>3</b>–<b>6</b> and <b>14</b> were determined by single-crystal X-ray diffraction analysis. In addition, jatrointelone K (<b>15</b>) was chemically transformed to euphoractine T (<b>8</b>) supporting the biosynthetic relationships between the two types of diterpenoids. Only compound <b>15</b> showed a moderate anti-CHIKV activity with an EC₅₀ value of 14 μM. Finally, using a molecular networking-based dereplication strategy, several close analogues of 12-<i>O</i>-tetradecanoylphorbol-13-acetate (TPA), one of the most potent inhibitors of CHIKV replication, were dereplicated

Structurally Diverse Diterpenoids from Sandwithia guyanensis

Bioassay-guided fractionation of an EtOAc extract of the trunk bark of Sandwithia guyanensis, using a chikungunya virus (CHIKV)-cell-based assay, afforded 17 new diterpenoids <b>1</b>–<b>17</b> and the known jatrointelones A and C (<b>18</b> and <b>19</b>). The new compounds included two tetranorditerpenoids <b>1</b> and <b>2</b>, a trinorditerpenoid <b>3</b>, euphoractines P-W (<b>4</b>–<b>11</b>), and euphactine G (<b>13</b>) possessing the rare 5/6/7/3 (<b>4</b>–<b>7</b>), 5/6/6/4 (<b>8</b>–<b>11</b>), and 5/6/8 (<b>13</b>) fused ring skeletons, sikkimenoid E (<b>12</b>), and jatrointelones J-M (<b>14</b>–<b>17</b>) possessing jatropholane and lathyrane carbon skeletons, respectively. Jatrointelones J (<b>14</b>) and M (<b>17</b>) represent the first naturally occurring examples of C-15 nonoxidized lathyrane-type diterpenoids. The structures of the new compounds were elucidated by NMR spectroscopic data analysis. The relative configuration of compound <b>16</b> and the absolute configurations of compounds <b>3</b>–<b>6</b> and <b>14</b> were determined by single-crystal X-ray diffraction analysis. In addition, jatrointelone K (<b>15</b>) was chemically transformed to euphoractine T (<b>8</b>) supporting the biosynthetic relationships between the two types of diterpenoids. Only compound <b>15</b> showed a moderate anti-CHIKV activity with an EC₅₀ value of 14 μM. Finally, using a molecular networking-based dereplication strategy, several close analogues of 12-<i>O</i>-tetradecanoylphorbol-13-acetate (TPA), one of the most potent inhibitors of CHIKV replication, were dereplicated

Structurally Diverse Diterpenoids from Sandwithia guyanensis

Bioassay-guided fractionation of an EtOAc extract of the trunk bark of Sandwithia guyanensis, using a chikungunya virus (CHIKV)-cell-based assay, afforded 17 new diterpenoids <b>1</b>–<b>17</b> and the known jatrointelones A and C (<b>18</b> and <b>19</b>). The new compounds included two tetranorditerpenoids <b>1</b> and <b>2</b>, a trinorditerpenoid <b>3</b>, euphoractines P-W (<b>4</b>–<b>11</b>), and euphactine G (<b>13</b>) possessing the rare 5/6/7/3 (<b>4</b>–<b>7</b>), 5/6/6/4 (<b>8</b>–<b>11</b>), and 5/6/8 (<b>13</b>) fused ring skeletons, sikkimenoid E (<b>12</b>), and jatrointelones J-M (<b>14</b>–<b>17</b>) possessing jatropholane and lathyrane carbon skeletons, respectively. Jatrointelones J (<b>14</b>) and M (<b>17</b>) represent the first naturally occurring examples of C-15 nonoxidized lathyrane-type diterpenoids. The structures of the new compounds were elucidated by NMR spectroscopic data analysis. The relative configuration of compound <b>16</b> and the absolute configurations of compounds <b>3</b>–<b>6</b> and <b>14</b> were determined by single-crystal X-ray diffraction analysis. In addition, jatrointelone K (<b>15</b>) was chemically transformed to euphoractine T (<b>8</b>) supporting the biosynthetic relationships between the two types of diterpenoids. Only compound <b>15</b> showed a moderate anti-CHIKV activity with an EC₅₀ value of 14 μM. Finally, using a molecular networking-based dereplication strategy, several close analogues of 12-<i>O</i>-tetradecanoylphorbol-13-acetate (TPA), one of the most potent inhibitors of CHIKV replication, were dereplicated