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Analysis of Target Molecular and Preparation of Molecular Probes for Neurotrophic Low-Molecular Natural Products

神经营养性低分子天然产物的靶分子分析及分子探针的制备

基本信息

批准号：
16510172
负责人：
FUKUYAMA Yoshiyasu
金额：
$ 2.43万
依托单位：
Faculty of Pharmaceutical Sciences, 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：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

This research project has been carried out aiming at search for new neurotrophic natural products and synthesis of the three known active compounds, honokiol, neovibsanin an talaumidin as well as for clarifying their neurotrophic mechanism. The following results have been obtained.(1)Screening natural products by using PC 12 cells has resulted in the discovery of five new active compounds, one of which is an ergosterol bearing an endoperoxide. This compound not only promotes significantly neurite outgrowth of PC 12, but also exhibits neurotrophic activity in the primary cultured rat cortical neurons. Another four neovibsanins have been isolated as neurotrophic substances from Viburnum sieboldii.(2)Honokiol has been synthesized by palladium-catalyzed Suzuki-Miyaura cross coupling as a key reaction. The structure units that are essential for neurotrophic activity have been identified. Several fluorescent derivatives attached to luminous groups (7-MCA or NBD) at the 3'-position were synth … More esized and then the distribution in neurons using them was investigated. Consequently, it was found that the fluorescent derivatives penetrated into the neuron and concentrated on the connecting region to the neurite. The competitive experiment between honokiol and the fluorescent derivatives suggest that the fluorescent derivatives of honokiol are likely to interact at the same site in the neurons as honokiol. These results indicate that honokiol can penetrate into the neuron and interacts at some specific proteins such as the enzyme.(3)The enantioselective synthesis of talaumidin has been accomplished by asymmetric Evans protocol, stereoselective hydroboration and highly controlled Firedel-Crafts arylation. This synthesis led to the conclusion of the absolute configuration of (2S,3S,4S,5S)-talaumidin, and allowed us to prepare its possible stereoisomers for structure-activity relationship.(4)Applying tandem Pd-catalyzed Heck and Trost reactions towards a diene system has developed the construction of the cyclohexane ring core fused with a tetrahydrofuran ring. This new methodology will be used for synthesis of neovibsanins. Less

本研究旨在寻找新的神经营养天然产物，合成和厚朴酚、新维布散宁和他劳米定三种已知活性化合物，并阐明其神经营养机制。取得了以下结果。（1）利用PC 12细胞筛选天然产物，发现了五种新的活性化合物，其中之一是带有内过氧化物的麦角甾醇。该化合物不仅能显著促进PC 12的突起生长，而且对原代培养的大鼠皮层神经元具有神经营养活性。另外四种新荚孢素是从天女荚中分离得到的神经营养物质。（2）以钯催化Suzuki-Miyaura偶联反应为关键反应合成了和厚朴酚。神经营养活性所必需的结构单元已被确定。合成了几种3 ′-位发光基团（7-MCA或NBD）的荧光衍生物， ...更多信息测量，然后研究使用它们的神经元中的分布。因此，发现荧光衍生物渗透到神经元中并集中在与神经突的连接区域。和厚朴酚与荧光衍生物之间的竞争实验表明，和厚朴酚的荧光衍生物可能与和厚朴酚在神经元中的同一位点相互作用。这些结果表明和厚朴酚可以渗透到神经元中并与酶等一些特定蛋白质相互作用。（3）通过不对称Evans反应、立体选择性硼氢化反应和高度可控的Firedel-Crafts芳基化反应实现了他劳脒的对映选择性合成。通过对（2S，3S，4S，5S）-talaumidin的合成，确定了其绝对构型，并制备了其可能的立体异构体，进行了构效关系研究。（4）将Pd催化的Heck和Trost反应串联应用于二烯体系，开发了与四氢呋喃环稠合的环己烷环核的结构。这种新的方法将用于合成neovibsanins。少

项目成果

期刊论文数量（60）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Synthetic studies toward merrilactone A: a short synthesis of AB ring motif

DOI：
10.1016/j.tetlet.2005.08.116
发表时间：
2005-10-24
期刊：
TETRAHEDRON LETTERS
影响因子：
1.8
作者：
Harada, K;Kato, H;Fukuyama, Y
通讯作者：
Fukuyama, Y

Protective Effect of 5-Lipoxygenase Inhibitor Ardisiaquinone A on Hepatic Ischemia-reperfusion Injury in Rats.

5-脂氧合酶抑制剂紫金牛醌 A 对大鼠肝缺血再灌注损伤的保护作用。

DOI：
发表时间：
2005
期刊：
Planta Medica 71
影响因子：
0
作者：
Y.Shigeri;K.Shimamoto;Shinichi Miyairi;Y.Fukuyama et al.
通讯作者：
Y.Fukuyama et al.

Cyclovibsanins, Unprecedented Seven-Membered Vibsane-type Diterpenoids from Viburnum awbuki.

环维沙宁 (Cyclovibsanins)，一种来自荚蒾 awbuki 的前所未有的七元 Vibsane 型二萜类化合物。

DOI：
发表时间：
2004
期刊：
Letters in Organic Chemistry 1・2
影响因子：
0
作者：
I.Abe*;Y.Sakano;M.Sodeyama;H.Tanaka;H.Noguchi;M.Shibuya;Y.Ebizuka;Hisashi Matsuda;Kotaro Okajima;Yoshiyasu Fukuyama et al.
通讯作者：
Yoshiyasu Fukuyama et al.

Neurotrophic Effects of Talaumdin, a Neoliganan from Aristolochia arcuata, in Primary Cultured Rat

Talaumdin（一种来自马兜铃的新木脂素）对原代培养大鼠的神经营养作用

DOI：
发表时间：
2004
期刊：
Planta Medica 70・7
影响因子：
0
作者：
H.Noma;H.Tanaka;H.Noguchi;M.Shibuya;Y.Ebizuka;I.Abe*;Yoshiyasu Fukuyama et al.
通讯作者：
Yoshiyasu Fukuyama et al.

Neurotrophic Effects of Talaumdin, from Aristolochia arcuata, in Primary Cultured Rat Cortical Neurons.

来自马兜铃的 Talaumdin 对原代培养的大鼠皮质神经元的神经营养作用。

DOI：
发表时间：
2004
期刊：
Planta Med. 70(7)
影响因子：
0
作者：
Tokura;K.;Tojo;M.;Kida;K.;Hoshino;T.and H.Kanda;Y.Fukuyama et al.;Y.Fukuyama et al.
通讯作者：
Y.Fukuyama et al.