Dynamic changes in composition of extracts of natural products as monitored by in situ NMR

The direct in situ NMR observation and quantification, based on the aldehyde -CH chemical shift region, of the inter-conversion of secoiridoid derivatives due to temperature and solvent effects is demonstrated in complex extracts of natural products without prior isolation of the individual components. The equilibrium between the aldehyde hydrate form and the dialdehyde form of the oleuropein aglycon of an olive leaf aqueous extract in D(2)O was shown to be temperature dependent. The resulting thermodynamic values of the Van't Hoff plot with ΔH(o) = -26.34 ± 1.00 kJ mol(-1) and TΔS° (298 K) = -24.70 ± 1.00 kJ mol(-1) demonstrate a significant entropy term which nearly compensates the effect of enthalpy at room temperature. The equilibrium between the two diastereomeric hemiacetal forms and the dialdehyde form of the oleuropein 6-O-β-d-glucopyranoside aglycon of an olive leaf aqueous extract in CD(3) OD was also shown to be strongly temperature dependent again because of the significant entropy term (TΔS° (298 K) = -26.50 ± 1.39 kJ mol(-1)) compared with that of the enthalpy term (ΔH(o) = -36.64 ± 1.46 kJ mol(-1)). This is the first demonstration of the significant role of the entropy parameter in determining the equilibrium of chemical transformations in complex mixtures of natural products due to solvent and temperature effects.