Learning Organic Chemistry from Bark Beetle Pheromone Biosynthesis

Frontalin, endo-brevicomin, and exo-brevicomin belong to a class of natural products known as 6,8-dioxabicyclo [3.2.1] octanes, and are bark beetle aggregation pheromones that are also found in elephant secretions and excretions. Biosynthesis in the beetles begins with achiral, acyclic enones and progresses via a series of steps comprised of stereoselective epoxidation, inversion of chirality via cyclization through an intramolecular Sn2 reaction, and closure of the final ring by way of nucleophilic collision of an alkoxide with an oxonium ion. Organic Chemistry students follow a series of steps using molecular models to discern the configuration of each chirality center as it is formed, as well as to understand how geometric constraints of epoxidation and the [3.2.1] bridged ring system preclude the formation of some of the theoretically possible stereoisomers. Students then use computer-based molecular modeling (Spartan) to enhance their 3-D visualization of these bridge-ringed pheromones. These activities use biologically and chemically interesting pheromones to relate 2-D molecular structures to their 3-D counterparts, thereby inculcating a better understanding of a number of stereochemical concepts and also illustrating that the understanding of a biochemical synthesis relies on many of the same organic chemistry concepts that they are studying in class.