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

[GRAPHICS] 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 H-1 and C-13 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.