Bioinspired Total Synthesis of Mulberrofurans G and J, Inethermulberrofuran C, and Mongolicin C from a Common Intermediate

The bioinspired total synthesis of mulberry Diels-Alder adducts (MDAAs) mulberrofuran G (<b>4</b>) and J (<b>20</b>), inethermulberrofuran (<b>5</b>), and mongolicin C (<b>6</b>) from the common synthetic intermediate <b>9</b> is reported. The approach involved the synthesis of the protected diene <b>9</b> and orthogonally protected dienophile <b>17</b> followed by H-bond-assisted Diels-Alder reaction to produce the <i>endo</i>-adduct <b>18</b> as well as the <i>exo</i>-adduct <b>19</b> (60% yield, 1.2:1 ratio). Treatment of the <i>endo</i> isomer <b>18</b> with 10% H₂SO₄ in EtOH at 60 °C gave mulberrofuran G (<b>4</b>) as the major product along with a trace of inethermulberrofuran C (<b>5</b>), while exposure of the same isomer to 3 M HCl in MeOH at 80 °C gave <b>5</b> as the major product. An intramolecular oxidative cyclization of the phenol <b>7</b> and acid-induced deprotection yielded the proposed structure for mongolicin C (<b>6</b>). In addition, acid deprotection of <i>exo</i>-isomer <b>19</b> gave mulberrofuran J (<b>20</b>) in low yield.