Synthesis and Toxicity to Mammalian Cells of the Carrot Dihydroisocoumarins

The dihydroisocoumarins (+/-)-6-methoxy-8-hydroxy-3-methyl-3,4-dihydroisocoumarin (1), (+/-)-6,8-dihydroxy-3-methyl-3,4-dihydroisocoumarin (2), and (+/-)-6,8-dimethoxy-3-methyl-3,4-dihydroisocoumarin (3) were synthesized with high yields via metalation of o-methylbenzamides. The toxicity of these compounds and that of (-)-1 extracted from carrot cells were tested, in vitro, on Chinese hamster cells. The toxicity was determined according to the presence or absence of a hydroxyl group in the peri position of the lactonic carbonyl group and according to the stereochemistry of the dihydroisocoumarin.