Total Synthesis of Three Classes of Ring C-seco Limonoids

The nimbin-type, salannin-type and nimbolinin-type are three structurally related classes of ring C-seco limonoids possessing a complicated hexacyclic framework with a broad range of biological activities. Herein, a convergent and divergent route to access these classes was disclosed by the efficient and protecting-group-free syntheses of 52 ring C-seco limonoids. Key transformations include: 1) a catalytic asymmetric intermolecular Diels-Alder reaction to forge the A-ring bearing desired stereochemistry at C4 and C5; 2) a diastereoselective Pd-catalyzed reductive Heck reaction for the formation of the C8-C9 bond; 3) a sulfonyl hydrazone-mediated etherification and a regioselective 5-exo-trig radical cyclization for construction of the central tetrahydrofuran ring of the natural products; 4) BF3·Et2O-promoted biomimetic skeletal rearrangement reaction of the salannin-type to generate the nimbolinin-type.