Chemical Studies toward Development of Nerve Cell Degeneration Repairing or Protecting Agent

神经细胞变性修复或保护剂开发的化学研究

• 批准号: 09680582
• 负责人: FUKUYAMA Yoshiyasu
• 金额: $ 2.18万
• 依托单位: Tokushima Bunri University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680582/
• 关键词: neurotrophic substance; culture of fetat rat neuron; limonoid; terpene; aromatic compound; palladium; plant tissue culture; HRP; 神経栄養因子; フロログルシン

This research project has been performed toward development of nerve cell degeneration repairing and/or protecting agent from novel neurotrophic natural products. The following results have been obtained.(1) An unprecedented macrocyclic vibsane-type diterpene bearing an endo-peroxide in the molecule and novel limonoids were isolated as new neurotrophic active substances from the leaves of Viburnum awabuki and the roots of Melia azedarach Linn ver. Japonica, respectively.(2) The first synthesis of plagiochin A, a 16-membered bis(bibenzyl) which is one of the potent neurotrophic natural products has been accomplished by an intramolecular Pd(O)-catalyzed Still-Kelly reaction. Another neurotrophic sesquiterpenes dimers, mastigophorenes A and B have been obtained by oxidative phenol coupling of (+)-herebertendiol, which was already synthesized by applying an intramolecular Heck reaction to the construction of the quaternary carbon center linked to the benzene ring. The extremely simple syntheses of neurotrophic active substnaces, americanol A and isoamericanol A which were isolated from Phytolacca americana have been performed by HRP-catalyzed oxidative dimerization of caffeic acid.(3) Plant tissue culture has been applied to produce americanol A and isoamericanol A in the callus of Phytolacca americana, but their formation has not been so far realized. The callus successfully induced from the seeds of Belamcanda chinensis is now subjected to study on the condition of liquid culture. We will continue working on the production and biotransformation of neurotrophic active substances by using the plant tissue culture.(4) Apotosis system in the cell culture of fetal rat cerebral hemisphere has been modified, and thereby we will be able to screen natural products which inhibit the apotosis of the nerve cell induced by beta-amyloid protein.

本研究旨在开发新型神经营养天然产物的神经细胞变性修复和/或保护剂。主要研究结果如下：(1)从紫花木的叶和苦荞的根中分离得到了一种新的具有神经营养活性的新型柠檬苦素类化合物。(2)通过分子内Pd(O)催化的Sist-Kelly反应，首次合成了具有神经营养作用的天然产物--16元双(联苯基)斜坡菌素A。另一种具有神经营养作用的倍半萜二聚体马斯替卜烯A和B是通过(+)-异丁烯二醇的氧化苯酚偶联反应合成的，它是通过分子内Heck反应构建与苯环相连的四元碳中心而合成的。用HRP催化咖啡酸氧化二聚法合成了从商陆中分离得到的神经营养活性物质美洲醇A和异美洲醇A。(3)植物组织培养已被应用于商陆愈伤组织中合成美洲醇A和异美洲醇A，但至今尚未实现它们的形成。现对射干种子成功诱导出的愈伤组织进行液体培养条件的研究。我们将继续利用植物组织培养对神经营养活性物质的生产和生物转化进行研究。(4)对胎鼠大脑半球细胞培养中的细胞凋亡系统进行了改造，从而能够筛选出抑制β-淀粉样蛋白诱导神经细胞凋亡的天然产物。

项目成果

Yoshiyasu Fukuyama: "Synthetic Studies on Neurotrophic Isocuparane- Type Dimers, Mastigophorenes, Isolated from the Liverwort Mastigophora diclados" Phytomedcine. 3・Suppl.1. 250-252 (1997)

Yoshiyasu Fukuyama：“从地钱 Mastigophora diclados 中分离出的神经营养性异螟烷型二聚体的合成研究”Phytomedcine 3·Suppl.1 (1997)。

Hiroyuki Minami: "Xanthones and Benzophenone from Garcinia subelliptica." Phytochemistry. 49.6. 1783-1785 (1998)

Hiroyuki Minami：“来自亚椭圆形藤黄果的氧杂蒽酮和二苯甲酮。”

Yoshiyasu Fukuyama et al.: "Structures of New 7-Membered Ring Vibsane-type Diterepenes Isolated from Leaves of Viburnum awabuki." Chem.Pharm.Bull.46, (8). 1194-1198 (1998)

Yoshiyasu Fukuyama 等人：“从荚蒾叶子中分离出的新七元环 Vibsane 型二萜的结构”。

Yoshiyasu Fukuyama et al.: "Garsubellins, Polyisoprenylated Phlorogulcin Derivatives from Garcinia subelliptica." Phytochemistry. 49, (3). 853-857 (1998)

Yoshiyasu Fukuyama 等人：“Garsubellins，来自 Garcinia subelliptica 的聚异戊二烯化苯丙素衍生物”。

Yoshiyasu Fukuyama: "Garsubellins, Polyisoprenylated Phlorogulcin Derivatives from Garcinia subelliptica." z z Phytochemistry. 49.3. 853-857 (1998)

Yoshiyasu Fukuyama：“Garsubellins，来自 Garcinia subelliptica 的聚异戊二烯化苯丙素衍生物。”