Synthesis and antibacterial evaluation of typharin analog: 6,8-dihydroxy-7-methyl-3-styryl-3,4-dihydroisocoumarin

Abstract

Synthesis of the 6-hydroxy-7-methyl analog of typharin (8-dihydroxy-3-styryl-3,4-dihydroisocoumarin) isolated from the rhizomes of Typha capensis has been described. Direct condensation of 3,5-dimethoxy-4-methylhomophthalic acid (1) with cinnamoyl chloride at elevated temperature under inert conditions afforded 6,8-dihydroxy-7-methyl-3-styrylisocoumarin (2). Hydrolysis of isocoumarin to keto acid (3) followed by reduction and cyclodehydration of hydroxy acid analog (4) afforded ( ± )-6,8-dimethoxy-3-(4-methoxyphenyl)-3,4-dihydroisocoumarin (5). Demethylation of the latter using anhydrous aluminum chloride/ethane thiol furnished the title isocoumarin (6). Compounds (1–6) were screened for in vitro antibacterial activity against a representative panel of Gram-positive and Gram-negative bacteria using levofloxacin as the reference drug.

Keywords:

• dihydroisocoumarin
• Typha capensis
• typharin
• antibacterial