Synthesis and Applications of Terpenoid Natural Products: Total Synthesis of Scabrolide A and Havellockate, and Synthesis of Pinene Oxidation Products for Atmospheric Investigations

Citation

Hafeman, Nicholas Joseph (2022) Synthesis and Applications of Terpenoid Natural Products: Total Synthesis of Scabrolide A and Havellockate, and Synthesis of Pinene Oxidation Products for Atmospheric Investigations. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/3st9-6a73. https://resolver.caltech.edu/CaltechTHESIS:06032022-194915019

Abstract

The total synthesis of complex natural products remains one of the enduring challenges in organic chemistry. Whether motivated by the biological activity of the target, or its structural complexity, total synthesis continues to serve as a proving ground for synthetic methodology as well as strategic planning. Herein is described the first total synthesis of the polycyclic furanobutenolide-derived (nor)cembranoid diterpenoids scabrolide A and havellockate. Our total synthesis of scabrolide A involves an intramolecular [4+2] cycloaddition, which forges a fused [5–5–6] tricycle possessing two of the three carbocycles that characterize the natural product. Next, a photocycloaddition/fragementation sequence is employed to forge the final seven-membered ring and complete the total synthesis. Using a similar strategy, we could forge the [5–5–6] tricyclic core of the related diterpenoid havellockate with an intramolecular [4+2] cycloaddition. This is followed by a challenging enone allylation which installs the final carbon atoms of the target. Finally, elaboration of the allyl group, followed by a Cu/TEMPO-catalyzed oxidative lactonization furnishes havellockate. The final chapter of this thesis describes the synthesis and characterization of several pinene oxidation products and their dimers, which have been observed in pinene-derived secondary organic aerosol samples, as standards for atmospheric studies. This research uses the power of chemical synthesis to confirm (and in some cases reassign) the structures of naturally occurring, yet difficult to characterize chemical species found in the atmosphere.

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