Determination of the preferred conformation of the bicyclic Galerucella pheromone using density functional theory optimization and calculations of chemical shifts.

A pheromone from the beetle, Galerucella calmariensis, was recently isolated and identified (Bartelt, R. J. et al. J. Chem. Ecol. 2006, 32, 693-712) as a 14-carbon, bicyclic dimethylfuran lactone, with the systematic name 12,13-dimethyl-5,14-dioxabicyclo[9.2.1]tetradeca-1(13),11-dien-4-one. The main 12-membered lactone ring is very flexible; as a result, there exist multiple possible conformations. The preferred conformation cannot be deduced solely from room-temperature NMR measurements. Using density functional (DFT) studies, 26 unique conformers with energies within 10.0 kcal/mol of the global minimum-energy structure were found. A mirror-image plane exists so that each conformer has an "inverse" structure with the same energy, for which the dihedral angles around the flexible ring have opposite sign. The isotropic 1H and 13C NMR chemical shifts of the DFT-optimized structures were calculated using the gauge-including atomic orbital (GIAO) method. By considering the relative energies of the conformers and the calculated and observed NMR spectra, we concluded that the molecule exists primarily as a mixture of two distinct conformers at room temperature, each being present with its mirror-image inverse. Structural interconversions among these likely occur on a time scale that is fast compared to the NMR experiments. Using mode-following and dihedral-driving techniques, several potential pathways were found for the conversion of the lowest-energy conformer to its mirror-image structure. Ab initio molecular dynamics (AIMD) using the 4-31G basis set was carried out for 50 ps to test the availability of various low-energy minima and the transition states found from the searches noted above.