title: Systematic Asymmetric Synthesis of All Diastereomers of (-)-Talaumidin and Their Neurotrophic Activity.
abstract: (-)-Talaumidin (1), a 2,5-biaryl-3,4-dimethyltetrahydrofuran lignan isolated from Aristolochia arcuata Masters, shows significant neurite-outgrowth promotion and neuroprotection in primary cultured rat cortical neurons and in NGF-differentiated PC12 cells. The four stereogenic centers on the tetrahydrofuran moiety in 1 result in the presence of seven diastereomers except for their enantiomers. In order to investigate the stereochemistry-activity relationships of the stereoisomers, the systematic synthesis of all stereoisomers of 1 was accomplished by employing Evans aldol, diastereoselective hydroboration, reductive deoxygenation, and Mitsunobu reactions as key steps. The ability of all of the synthesized stereoisomers to promote neurite-outgrowth in PC12 and neuronal cells was evaluated. All stereoisomers exhibited moderate to potent neurotrophic activities in NGF-differentiated PC12 cells at 30 μM and in primary cultured rat cortical neuronal cells at 0.01 μM. In particular, 1e bearing all cis substituents resulted in the most potent neurite-outgrowth promotion.
authors.affiliation: †Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Yamashiro-cho, Tokushima 770-8514, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.affiliation: †Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Yamashiro-cho, Tokushima 770-8514, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Kubo
authors.affiliation: †Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Yamashiro-cho, Tokushima 770-8514, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Horiuchi
authors.affiliation: †Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Yamashiro-cho, Tokushima 770-8514, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Ishii
authors.affiliation: †Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Yamashiro-cho, Tokushima 770-8514, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Esumi
authors.affiliation: ‡Faculty of Education, Gunma University, Maebashi, Gunma 371-8510, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hioki
authors.affiliation: †Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Yamashiro-cho, Tokushima 770-8514, Japan.
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Fukuyama
mesh_terms: D000818:Animals; D030022:Aristolochia / Q000737:chemistry*; D002454:Cell Differentiation; D002460:Cell Line; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D017705:Lignans / Q000737:chemistry*; D009414:Nerve Growth Factors / Q000737:chemistry*; D009474:Neurons / Q000737:chemistry*; D016716:PC12 Cells / Q000737:chemistry* / Q000187:drug effects; D051381:Rats; D013237:Stereoisomerism
chemical_list: D005663:Furans; D017705:Lignans; D009414:Nerve Growth Factors; C492479:talaumidin; C018674:tetrahydrofuran