A full set of 8,4′-oxy-8′-phenylneolignan stereoisomers from Sophora tonkinensis and their absolute configurations by TDDFT

Abstract

A full set of 8,4′-oxy-8′-phenylneolignans with four chiral carbons, named (+)/(−)-leptolepisols D1‒D2 and (+)/(−)-sophorols A‒F, were isolated from the roots and rhizomes of Sophora tonkinensis Gagnep., including 14 previously undescribed stereoisomers, along with 2 known leptolepisol D diastereomers. Their planar structures and relative configurations were elucidated by detailed spectroscopic analysis (HRESIMS and NMR). Based on a highly accurate conformer filtering protocol at low computational cost, the absolute configurations of full set 8,4′-oxy-8′-phenylneolignans were completely assigned by TDDFT calculations of ECD spectra for the first time. Furthermore, (+)/(−)-sophorol A, (−)-sophorol B, and (−)-sophorol E could moderately suppress the lipopolysaccharide-induced nitric oxide production in murine macrophages at 10 μM, with inhibitory ratios of 48.4–52.9%.