Chiral resolution, absolute configuration of two pairs of unusual monoterpene enantiomers from Eupatorium fortunei

Two unusual monoterpene racemates, (±)-eupafortin A (1) and (±)-eupafortin B (2), were isolated from the aerial parts of Eupatorium fortunei. Subsequent chiral resolution led to the separation of two pairs of enantiomers, (+)- (1a) and (–)-eupafortin A (1b), (+)- (2a) and (–)-eupafortin B (2b), respectively. Their structures including absolute configurations were deduced based on spectroscopic analyses and ECD calculations. The isolated compounds are the first example of monoterpenes possessing benzocyclobutene skeleton in natural products and a plausible biogenetic pathway for them was proposed. These compounds exhibited moderate inhibitory activity against nitric oxide (NO) production in lipopolysaccharide-induced (LPS) RAW 264.7 macrophage cells.