Résumé
A new class of potent liver injury protective compounds, phychetins A-D ( 1- 4) featuring an unique 6/6/5/6/5 pentacyclic framework, were isolated and structurally characterized from a Chinese medicinal plant Phyllanthus franchetianus. Compounds 2- 4 are three pairs of enantiomers that were initially obtained in a racemic manner, and were further separated by chiral HPLC preparation. Compounds 1- 4 were proposed to be originated biosynthetically from a coexisting lignan via an intramolecular Friedel-Crafts reaction as the key step. A bioinspired total synthesis strategy was thus designated, and allowed the effective syntheses of compounds 2- 4 in high yields. Some of compounds exhibited significant anti-inflammatory activities in vitro via suppressing the production of pro-inflammatory cytokine IL-1β. Notably, compound 4, the most active enantiomeric pair in vitro, displayed prominent potent protecting activity against liver injury at a low dose of 3 mg/kg in mice, which could serve as a promising lead for the development of acute liver injury therapeutic agent.
Résumé
A new sesquiterpenoid and two pregnane steroids, named vernobockolide C (1) and vernobockones A and B (2 and 3), respevtively, along with a known sesquiterpenoid, 7, 10-epoxy-11-hydroxy-bisabol-2-en-15-al, were isolated from the aerial part of Vernonia bockiana. Their structures were elucidated on the basis of extensive spectroscopic data analysis, especially 2D NMR (HSQC, HMBC, and ROESY). This study further expands the chemical space of this underexplored species.