Bioorganic & Medicinal Chemistry Letters 2004-05-17

Efficient synthesis and structure-activity relationship of honokiol, a neurotrophic biphenyl-type neolignan.

Tomoyuki Esumi, Gouki Makado, Haifeng Zhai, Yasuhiro Shimizu, Yasuhide Mitsumoto, Yoshiyasu Fukuyama

Index: Bioorg. Med. Chem. Lett. 14(10) , 2621-5, (2004)

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Abstract

Honokiol, a biphenyl-type neolignan, which shows the remarkable neurotrophic effect in primary cultured rat cortical neurons, has been effectively synthesized in 21% yield over 14 steps starting from 5-bromosalicylic acid and p-hydroxybenzoic acid by utilizing Pd-catalyzed Suzuki-Miyaura coupling reaction as a key step. Additionally, the structure-activity relationship between neurite outgrowth-promoting activity and its O-methylated and/or its hydrogenated analogues was examined in the primary cultures of fetal rat cortical neurons, suggesting that 5-allyl and 4'-hydroxyl groups are essential for affecting the neurotrophic activity of honokiol.