Concise Syntheses of ent-Aquilanol A and Aquilanol B via Retro-cycloisomerization of (-)-Caryophyllene Oxide. Access to Medium-sized Oxygenated Carbocyclic Scaffolds

Abstract

The first concise synthesis of naturally occurring aquilanols A and B, two unprecedented 7/10 bicyclic sesquiterpenoids, is present-ed. Key features of the synthesis are a retrocycloisomerization event on (-)-caryophyllene oxide to form the eleven-membered car-bocyclic frame and an intramolecular epoxide opening to construct the bicyclic skeleton. The latter provides evidence to plausible biosynthesis of natural compounds, rendering our synthesis biomimetic. Our plan provides selectively access to other medium-sized carbocyclic oxygenated compounds, thus enhancing the structural diversity of final products.

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

“…Given the interest of our group in the synthesis of low-molecular weight antibacterial agents, combined with the challenging structural features of aquilanols A ( 1 ) and B ( 2 ), we embarked on the synthesis of the compounds mentioned above. Our interest grew upon noticing that no total synthesis has yet been reported and that the price of agarwood, the natural source of aquilanols, is exceptionally high and continues to increase due to depletion of the Aquilaria tree population…”