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

  • Bioorg Med Chem Lett. 2004 May 17;14(10):2621-5. doi: 10.1016/j.bmcl.2004.02.067.
Tomoyuki Esumi  1 ,  Gouki Makado ,  Haifeng Zhai ,  Yasuhiro Shimizu ,  Yasuhide Mitsumoto ,  Yoshiyasu Fukuyama
Affiliations
  • 1. Institute of Pharmacognosy, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan.
PMID: 15109665 DOI: 10.1016/j.bmcl.2004.02.067
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.

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