Stereochemical elucidation of natural products using the novel NOE quantification combined with ⁿJ_H-H and ⁿJ_C-H...

Natural products such as polyketides often possess spin systems consisting of a methine group directly bonded to a methyl group (e.g. -CH_a(OH)-CH_b(CH₃)-CH_c(OH)-). The methine proton H_b splits into a broadened multiplet by coupling with several vicinal protons, such as H_a and H_c, rendering the analysis of ⁿJ_C-H and ⁿJ_H-H with respect to H_b difficult using conventional NMR techniques. In this case, the stereochemical analysis of the aforementioned chain structure is generally hard due to the limited information of ⁿJ_C-H and ⁿJ_H-H. In order to obtain a more accurate analysis, we applied a novel NOE quantification, in which the NOE signal between H_b and CH₃ in the aforesaid spin system is used as a reference in a 1D double pulsed field gradient spin echo (DPFGSE)-NOESY spectra. The combinational analysis of the proposed NOE quantification together with ⁿJ_C-H and ⁿJ_H-H provided a reliable determination of stereochemistry of the sidechain in portmicin.