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

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 (1H/13C) 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.