Chem. Pharm. Bull., 51(12),1377-1381, December 2003

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Structures of 1,4-Benzodioxane Derivatives from the Seeds of Phytolacca americana and Their Neuritogenic Activity in Primary Cultured Rat Cortical Neurons

Hironobu TAKAHASI, Kazue YANAGI, Masumi UEDA, Kousuke NAKADE, and Yoshiyasu FUKUYAMA^*

Institute of Pharmacognosy, Faculty of Pharmaceutical Sciences, Tokushima Bunri University; Yamashiro-cho, Tokushima 770-8514, Japan. * To whom correspondence should be addressed. e-mail: fukuyama@ph.bunri-u.ac.jp

The methanol extract of the seeds of Phytolacca americana was reinvestigated to yield three new 1,4-benzodioxane-type compounds, americanoic acid methyl ester (1), isoamericanoic acid A methyl ester (2), and 9′-O-methylamericanol A (3) along with the previously isolated neolignans 6-9. The structures of 1-3 were characterized by 2D NMR and long-range selective proton-decoupling (LSPD) techniques. The neuritogenic effects of compounds 1-3, and dicarboxilic acids 4 and 5, which had been previously synthesized with horseradish peroxidase-catalyzed oxidative coupling of caffeic acid, were examined in primary cultured rat cortical neurons. Americanoic acid A methyl ester (1) exhibited neurite outgrowth-promoting activity at concentration of 0.01-1.0 μM, whereas dicarboxilic acids 4 and 5 were found to induce neuritogenesis dose dependently at the concentrations from 0.1 μM to 10 μM.

Key words neolignan; 1,4-benzodioxane; neuritogenic activity; antioxidant; Phytolacca americana; Phytolaccaceae