Lignans from Schisandra sphenathera Rehd. et Wils. and semisynthetic schisantherin A analogues: Absolute configuration, and their estrogenic and anti-proliferative activity

A new dibenzocyclooctene-type lignan, named schisandrin A1 (1), together with nine known lignans (2–10), was isolated from the stems of Schisandra sphenathera. The structure of schisandrin A1, which contains a spirocyclic epoxy unit, was established by means of spectroscopic methods. The absolute configurations of schisandrin A1 (1) and schisantherin A (2) were determined by electronic circular dichroism (CD) and TDDFT calculations, with 2 further confirmed by X-ray crystallographic data. Ten new schisantherin A derivatives (11–20) and 6,7-secoschisantherol A (2b) were synthesized. In addition, natural lignans and semisynthetic schisantherin A derivatives showed the antiproliferative activity on four human cancer cell lines and Id1 (an inhibitor of DNA binding protein) and estrogenic potency. Compounds 5, 7, and 8 exhibited very potent estrogenic activity.

Graphical abstractSchisandrin A1 (1), a new dibenzocyclooctene lignan, was identified from Schisandra sphenathera. Natural lignans and semisynthetic schisantherin A derivatives were evaluated for their estrogenic and anti-proliferative activity.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A new dibenzocyclooctene lignan schisandrin A1 (1) was isolated from S. sphenathera. ► Absolute configurations of compounds 1 and 2 were determined by CD and TDDFT methods. ► Natural and semisynthetic lignans inhibited four human cancer cell lines and Id1. ► Compounds 5, 7, and 8 showed very potent estrogenic activity.