Baeckeins F-I, four novel C-methylated biflavonoids from the roots of Baeckea frutescens and their anti-inflammatory activities

Abstract

Baeckea frutescens is an aromatic shrub used in South China as an ornamental and as a spice. Four unusual C-methylated biflavonoids named baeckeins F-I (1-4) were isolated from the roots of B. frutescens. The baeckeins F-I possessed a unique carbon skeleton, a flavonol conjugated with a coumaronochromone molecule via the unusual linkages of C-2-C-8 and C-3-O-C-7. Their structures were elucidated by analysis of the 1D ((1)H/(13)C) and 2D NMR (HSQC/HMBC/NOESY) and HR-ESI-MS spectroscopic data, and the absolute stereochemistry for chiral carbons of C-2 and C-3 was established by CD spectrometry combined with quantum chemical calculations. Baeckeins F-I (1-4) were also evaluated for their anti-inflammatory activities by detecting the NO production of LPS-induced RAW264.7 murine macrophage cell line; baeckein I (4) with the β-d-glucose unit and configuration of (2R,3R) exhibited the highest NO inhibitory activity (IC50=15.2 μM), which was similar to that of the positive control indomethacin.

Keywords: Absolute configuration; Anti-inflammatory activity; Baeckea frutescens; Baeckeins F–I; C-methylated biflavonoid.