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

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