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-pyranchromene-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.