Abstract
We describe a novel strategy for synthesizing the CD bicyclic ether substructure of the fused polycyclic ether natural product brevenal. This product arises from a three-step sequence beginning with (1) regio- and diastereoselective iodoetherification of an acyclic diene-diol, followed by (2) alkene metathesis with an epoxyalkene synthon, concluding with (3) palladium-catalyzed cycloisomerization. Despite the modest yield and long reaction period for the cycloisomerization step, these studies provide valuable insights into the nature of byproducts generated and the mechanisms by which they form. This work demonstrates a portion of a larger synthetic strategy for constructing the pentacyclic core of brevenal from an acyclic precursor.
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Acknowledgements
This material is based upon work supported by the National Science Foundation under CHE-1362249. We also acknowledge the use of the Bruker AVANCE III HD 600 MHz NMR spectrometer, supported by NSF grant CHE-1531620.
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Dedication This work celebrates the breadth, the quality, and the impact of Prof. Samuel Danishefsky’s contributions to the science of natural products synthesis, and honors his thoughtful mentorship of the corresponding author.
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Setterholm, N.A., McDonald, F.E. Sequential exo-mode oxacyclizations for the synthesis of the CD substructure of brevenal. J Antibiot 72, 364–374 (2019). https://doi.org/10.1038/s41429-018-0124-1
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DOI: https://doi.org/10.1038/s41429-018-0124-1
