Enantiomeric Lignans and Neolignans from Phyllanthus glaucus: Enantioseparation and Their Absolute Configurations

Eight pairs of enantiomeric neolignans, norlignans, and sesquineolignans (1a/1b-8a/8b), together with five known neolignans (9a/9b and 10-12), have been isolated from 70% acetone extract of the whole plants of Phyllanthus glaucus Wall. (Euphorbiaceae). The racemic or partial racemic mixtures were successfully separated by chiral HPLC using different types of chiral columns with various mobile phases. Their structures were elucidated on the basis of extensive spectroscopic data. The absolute configurations of 2a/2b were determined by computational analysis of their electronic circular dichroism (ECD) spectrum, and the absolute configurations of other isolates were ascertained by comparing their experimental ECD spectra and optical rotation values with those of structure-relevant compounds reported in literatures. Compounds 4a/4b featured unique sesquineolignan skeletons with a novel 7-4'-epoxy-8'-8''/7'-2'' scaffold, consisting of an aryltetrahydronaphthalene and a dihydrobenzofuran moiety. The planar structures of compounds 2, 3, 7, and 8 were documented previously; however, their absolute configurations were established for the first time in this study. The antioxidant activities of 1a/1b-8a/8b were evaluated using DPPH free radical scavenging assay, and the results demonstrated that compounds 1b and 3b showed potent DPPH radical scavenging activities with IC50 values of 5.987 ± 1.212 and 9.641 ± 0.865 μg/mL, respectively.