Conformational properties of the germacradienolide 6-epidesacetyllaurenobiolide by theory and NMR analyses.

Knowing the conformational properties of 1(10),4-cyclodecadiene gamma-lactones is important because of the biogenetic and evolutionary implications on the different groups of sesquiterpene lactones. Despite their importance, there are no physicochemical data on the conformational dynamic and the potential energy surface associated with the conformational changes of the cyclodecadiene ring. Fischer's biogenetic theory on the origin of ambrosanolides and helenanolides has support in the results presented since the conformers that yield two groups of sesquiterpene lactones coexist in solution as demonstrated by dynamic NMR experiments. These results are important on the basis of Fischer's proposal that states that the biosynthesis of each group of pseudoguaianolides requires a specific enzyme to select the right conformer to start the electrophilic cyclization. The germacra-1(10),4-dien-12,8alpha-olides can exist as a mixture of four different conformations, [(15)D(5),(1)D(14)], [(15)D(5),(1)D(14)], [(15)D(5),(1)D(14)], and [(15)D(5),(1)D(14)], and it is also proposed that the configuration of trans-annular cyclization depends on the conformation of the precursor. The results of the study presented herein show that 6-epi-desacetyllaurenobiolide exists in solution at room temperature as a mixture of two stable conformers, [(15)D(5),(1)D(14)] and [(15)D(5),(1)D(14)], which are more stable due to the diminishing of the so-called allylic strain. Analysis of the potential energy surface associated with the conformational interchange showed two other conformers that are intermediaries in the equilibria between [(15)D(5),(1)D(14)]/[(15)D(5),(1)D(14)] and [(15)D(5),(1)D(14)]/[(15)D(5),(1)D(14)]. This indicates the presence of six different conformers participating in the global process instead of the four that have been proposed. The experimental values of DeltaH(++), DeltaG(++), DeltaH(conf), and DeltaG(conf) of the conformational exchange and those calculated at the mPW1B95/6-31+G(d,p) level of theory are very similar, indicating that such level of theory is adequate for the description of this conformational equilibrium.