Natural and synthetic 2,2-dimethylpyranocoumarins with antibacterial activity

A new efficient synthetic approach to the natural coumarins 5-hydroxyseselin (5), 5-methoxyseselin (3), and (+/-) cis-grandmarin (9) is described as well as the synthesis of some new derivatives in the 5-methoxyseselin series (10-15). The natural coumarins 7-hydroxyalloxanthyletin (6), alloxanthoxyletin (8), and dipetalolactone (7) have also been obtained as secondary products. The type of fusion of the pyrano ring in all cases has been established by 2D NMR spectroscopy. The compounds have been studied for their in vitro antibacterial activity, which has been compared with that of some previously synthesized seselin derivatives. The most active compounds were 3, 7, 8, 11, and 14. Some structure-activity relationships are discussed.