Efficient synthesis and structure-activity relationship of honokiol, a neurotrophic biphenyl-type neolignan.
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.
Esumi
Tomoyuki
T
Institute of Pharmacognosy, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan.
Makado
Gouki
G
Zhai
Haifeng
H
Shimizu
Yasuhiro
Y
Mitsumoto
Yasuhide
Y
Fukuyama
Yoshiyasu
Y
D000818:Animals; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005333:Fetus / Q000166:cytology; D017705:Lignans / Q000138:chemical synthesis* / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000138:chemical synthesis* / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D000498:Allyl Compounds; D010636:Phenols
D001713:Biphenyl Compounds; D017705:Lignans; D009414:Nerve Growth Factors; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols