Total Synthesis of Hybridaphniphylline B

摘要

Hybridaphniphylline B (1 ) is a Daphniphyllum alkaloid possessing 11 rings and 19 stereocenters. Here we report the first total synthesis of 1 featuring a late-stage intermolecular Diels–Alder reaction of a fully elaborated cyclopentadiene and asperuloside tetraacetate. The diene was prepared on the basis of a scalable route to daphnilongeranin B (4 ). Claisen rearrangement of an allyl dienol ether was exploited as a key step; the subtle variation of the substrate and use of protic solvents suppressed the undesired Cope rearrangement. Daphniyunnine E (6 ) and dehydrodaphnilongeranin B (7 ), two congeners of 4 , were also synthesized. The dienophile arose from (+)-genipin through glycosylation and lactonization. A one-pot protocol was developed for the diene formation and Diels–Alder reaction; one of the cycloadducts was converted into 1 through reductive desulfurization and global deacetylation.