An Energetic and Conformational Analysis of Germacranolide Sesquiterpene Lactones
Michael, Michelle R.
MetadataShow full item record
Sesquiterpene lactones, constituents of plants of the family Compositae, are one of the largest classes of naturally occurring organic compounds. The germacranolides are one of the largest classes of the sesquiterpene lactones. These compounds have shown marked biological activity, and have therefore become increasing studied by scientists. Up to this point there has been only one mechanism proposed to account for this high degree in activity. This is the alkylation of the exocyclic a-methylene group by the sulfur-containing groups on enzymes and other proteins via a Michael addition reaction. However, if this were the only mode of action at work, then all of the sesquiterpene lactones should have the same amount of activity. However, this is not the case. Therefore, some other factors must come into play. Using molecular modeling the structures of the eight conformational isomers of the germacranolide sesquiterpene lactones were built and analyzed. After gathering baseline data for the unsubstituted compounds, substituent groups were added to see if this had any major effect on the energy and conformation of the molecule that might account for differences in biological activity. The structures were analyzed in the gas phase as well as in solvent. Also, examples of real germacranolides found in nature were analyzed to see how their properties differed. For the functional groups that were chosen, it was found that there was no significant effect in the structure of any of the conformational isomers. There was, however, a change in the overall energy of the molecule when the substituents groups were added. The direction of this change depended on the group that was added. It was also found that the compounds were most energetically stable in solution.