Synthesis and antinociceptive activity of seselin derivatives

Natural product seselin and related derivatives with an angular pyranocoumarin skeleton were synthesized from 8-acetyl-7-hydroxycoumarins by condensation with acetone, reduction, and dehydration successively under mild conditions with total yield of >50%. Twelve seselin derivatives were tested by the writhing response assay induced by acetic acid at a dose of 40 mg·kg^-1. Seselin (4a) and 4,8,8-trimethyl-9,9-dihydro-pyran［2,3-f］chromene-2,10-dione (2b) showed obviously antinociceptive activity with inhibitory effect of 85% and 50%, respectively, more or quite potent than aspirin in the same assay, suggesting that seselin derivatives could be a novel kind of potential antinociceptive agents.