Reaction Development for the Total Syntheses of the Terpenoid Natural Products (+)-Psiguadial B, (+)-Rumphellaone A, and (–)-Isodocarpin

Citation

Beck, Jordan Casey (2019) Reaction Development for the Total Syntheses of the Terpenoid Natural Products (+)-Psiguadial B, (+)-Rumphellaone A, and (–)-Isodocarpin. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/78A5-K715. https://resolver.caltech.edu/CaltechTHESIS:05142019-181954795

Abstract

The de novo synthesis of bioactive natural products provides an opportunity to learn more about the mechanism of bioactivity and to develop novel chemistry that is of interest to the synthetic community. Herein, we describe our strategy for the total synthesis of the trans-fused cyclobutane containing meroterpenoid (+)-psiguadial B. Key to this strategy was the development of a photochemical Wolff Rearrangement with asymmetric ketene aminolysis. A palladium-catalyzed C–H alkenylation is used to build structural complexity, and we use two different epimerization strategies to perform an enantiodivergent synthesis of (+)-psiguadial B.

This strategy was explored further and applied to the synthesis of chiral cyclobutanes through a 1,2-difunctionalization strategy, wherein a C–H arylation forges one carbon-carbon bond and a subsequent decarboxylative cross-coupling enables functionalization at the adjacent carbon. This strategy enabled the asymmetric total synthesis of (+)-rumphellaone A in 9 steps.

This report also highlights the work we have conducted in the development of a unified strategy for the enmein-type ent-kauranoid natural product, (–)-isodocarpin. We detail our investigation of a convergent cross-electrophile coupling as a means to build the core of (–)-isodocarpin. We also discuss our development of a 1,2-addition/semi-Pinacol rearrangement strategy for the preparation of all-carbon quaternary centers, which can be elaborated to enmein-type ent-kauranoid natural product scaffolds.

Thesis Files