SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF INSIGNIN AND ITS 8-METHOXY- AND 6-DEMETHOXY DERIVATIVES

Abstract

A short and efficient synthesis of insignin (8-hydroxy-6-methoxy-3-heptyl- isocoumarin) (1), a metabolite of natural lichens, has been described. Reaction of 3,5-dimethoxyhomophthalic anhydride (2) with octanoyl chloride in the presence of 1,1,3,3-tetramethylguanidine (TMG) and triethyl amine afforded the 6,8-dimethoxy-3-heptylisocoumarin (3) in high yield. Regioselective demethylation of the latter using anhydrous aluminum chloride furnished the 8-hydroxy-6-methoxy-3-heptylisocoumarin (1) whereas, the complete demethylation of (3) yielded 6,8-dihydroxy-3-heptylisocoumarin (4). The isocoumarins (1, 3, and 4) were examined in vitro for antibacterial activity and were shown to exhibit moderate activity.

KEY WORDS: Isocoumarin, Insignin, Antibacterial, Porpidia glaucophaea, Haematomma pachycarpum, 3,5-Dimethoxyhomophthalic anhydride


Bull. Chem. Soc. Ethiop. 2006, 20(1), 83-87.