Exploring the Chemical Space Accessed by Chiral Pool Terpenes. The (-)-Caryophyllene Oxide Paradigm.

Terpenes represent a flourishing source of structural motifs that can be converted into several more complex architectures. Realization of such transformations in a concise and efficient manner adds great value to the starting material. Herein, we study the case of (-)-caryophyllene oxide and convert it into natural sesquiterpenoids (rumphellolide K, rumphellaone A, and antipacid A), thus expanding the chemical space accessed by its privilege structure.

Syntheses of -Aquilanol A and -Aquilanol B via Retro-Cycloisomerization of (-)-Caryophyllene Oxide. Access to Medium-Sized Oxygenated Carbocyclic Scaffolds.

The first syntheses of the enantiomers of naturally occurring aquilanols A and B, two unprecedented 7/10 bicyclic sesquiterpenoids, are presented. Key features are a retro-cycloisomerization event on (-)-caryophyllene oxide to formulate the 11-membered carbocycle and an intramolecular epoxide opening to construct the bicyclic skeleton. The latter provides evidence of the plausible biosynthesis of natural compounds, rendering our syntheses biomimetic.