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We provide a full account of our synthetic studies targeting the hexacyclic calyciphylline B-type alkaloids, a subfamily of the Daphniphyllum natural products. Following an initial set of synthetic strategies focused on constructing the piperidine core of the calyciphylline B-type framework via a 6π-azaelectrocyclization, as well as exploiting the reactivity of underexplored oxazaborinine heterocycles, we ultimately designed a highly functionalized acyclic precursor which underwent carefully orchestrated and efficient cyclizations to forge the architecturally complex natural product scaffold. Our efforts have culminated in the development of the first total synthesis of (-)-daphlongamine H, provided access to its C5-epimer, (-)-isodaphlongamine H, and led to structural revision of deoxyisocalyciphylline B.

We describe a symmetry-inspired synthetic approach that has enabled a short synthesis of delavatine A and a formal synthesis of incarviatone A, which are two likely biosynthetically related natural products. The indane core of these natural products was constructed through a cascade sequence involving five transformations that occur in a single pot. Leveraging symmetry has allowed us to trace both natural products back to a versatile building block, 3,5-dibromo-2-pyrone, and studies related to site-selective cross-coupling of this polyhalogenated heterocycle are described. In addition, our strategy gave access to a putative biogenetic precursor, from which the syntheses of both natural products were attempted.