Synthesis of antibacterial isocoumarins: Synthesis and antibacterial activity of 3-alkylisocoumarins and (dl)-3-alkyl-3,4-dihydroisocoumarins

3-Pentyl- and 3-undecylisocoumarins 2a,b have been conveniently prepared in high yields by direct condensation of acyl chlorides with homophthalic acid. Alkaline hydrolysis of 2a,b yields the corresponding ketoacids 3a,b. The latter are reconverted to 2a,b either by treatment with acetic anhydride or with slightly acidified methanol. Treatment of 3a,b with methyl iodide or dry methanol in the presence of a catalytic amount of sulfuric acid affords the methyl keto-esters 4a,b. (dl)-3,4-Dihydroisocoumarins 6a,b are obtained by reduction of 3a,b to the racemic hydroxyacids 5a,b followed by cyclodehydration using acetic anhydride. The isocoumarins 2a,b and dihydroisocoumarins 6a,b have been examined in vitro for their antibacterial activity. Compounds 2a and 6b show significant activity comparable to the standard antibiotics.