The first total synthesis of the norcembranoid diterpenoid scabrolide A is disclosed. The route begins with the synthesis of two chiral pool-derived fragments, which undergo a convergent coupling to expediently introduce all 19 carbon atoms of the natural product. An intramolecular Diels-Alder reaction and an enone-olefin cycloaddition/fragmentation sequence are then employed to construct the fused [5-6-7] linear carbocyclic core of the molecule and to complete the total synthesis. File list (3) download file view on ChemRxiv ScabrolideAManuscriptFinalDraft.pdf (479.10 KiB) download file view on ChemRxiv TOCGraphic.pdf (129.56 KiB) download file view on ChemRxiv ScabrolideSIFinal.pdf (13.10 MiB)
We utilize ab initio quantum mechanics calculations to evaluate a range of plausible mechanistic pathways for the unexpected formation of a [6−4−4] ring system from an enone− olefin photocycloaddition in the synthesis of (−)-scabrolide A, previously reported by our group. We present a mechanistic analysis that is consistent with all current experimental observations, including the photoexcitation, the C−C bond formation, and the associated chemo-and diastereoselectivity.
The complete account of the total syntheses of scabrolide A and yonarolide are disclosed. This article describes an initial approach involiving a bio-inspired macrocyclization/transannular Diels–Alder cascade, which ultimately failed due...
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