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

本研究项目旨在寻找新的神经营养性天然产物，合成三种已知的活性化合物：和厚朴酚、新维布沙宁和talaumidin，并阐明其神经营养性机制。(1)天然产物的筛选。使用 PC 12 细胞进行的产品发现了五种新的活性化合物，其中一种是带有内过氧化物的麦角甾醇，该化合物不仅能显着促进 PC 的神经突生长。 12，而且在原代培养的大鼠皮层神经元中也表现出神经营养活性。另外四种新维布桑宁作为神经营养物质从天花荚蒾中分离出来。(2)和厚朴酚是通过钯催化的 Suzuki-Miyaura 交叉偶联作为关键结构反应合成的。已鉴定出几种对神经营养活性至关重要的单位，其附着在发光基团（7-MCA 或 NBD）上。合成了3'位，然后研究了使用它们的神经元中的分布，发现荧光衍生物渗透到神经元中并集中在神经突的连接区域。荧光衍生物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一些特定蛋白质（例如，和厚朴酚）相互作用。 (3)通过不对称Evans方案、立体选择性硼氢化和高度控制的Firedel-Crafts芳基化反应完成了talaumidin的对映选择性合成，得到了(2S,3S,4S,5S)-talaumidin的绝对构型。，并允许我们制备其可能的立体异构体以实现结构-活性关系。(4)应用串联Pd催化的Heck和Trost反应来制备二烯系统开发了与四氢呋喃环稠合的环己烷环核的结构，这种新方法将用于合成新维布沙宁。

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）

Neurtrophic Effect of Magnolol in the Hippocampal CA1 Region of Senescence-Accelerated Mic (SAMP1).

厚朴酚对衰老加速麦克风 (SAMP1) 海马 CA1 区的神经营养作用。

DOI：
发表时间：
2005
期刊：
Biol. Pharm. Bull. 28・9
影响因子：
0
作者：
Ishihara;S.;Shiibashi;T.;Sato;Y.;Murata;K.;Nogami;S.;Uyama Tomohiko;宇山智彦;Uyama Tomohiko;Uyama Tomohiko;Uyama Tomohiko;Uyama Tomohiko;Yoshiyasu Fukuyama et al.;Yoshiyasu Fukuyama et al.
通讯作者：
Yoshiyasu Fukuyama et al.

Neurotrophic Effects of 1,4,Diaryl-2,3-dimethyltetrahydrofuran Lignans.

1,4,二芳基-2,3-二甲基四氢呋喃木脂素的神经营养作用。

DOI：
发表时间：
2005
期刊：
Biol.Pharm.Bull 27・2
影响因子：
0
作者：
Ishihara;S.;Shiibashi;T.;Sato;Y.;Murata;K.;Nogami;S.;Uyama Tomohiko;宇山智彦;Uyama Tomohiko;Uyama Tomohiko;Uyama Tomohiko;Uyama Tomohiko;Yoshiyasu Fukuyama et al.;Yoshiyasu Fukuyama et al.;Y.Fukuyama et al.;Yoshiyasu Fukuyama et al.
通讯作者：
Yoshiyasu Fukuyama et al.

トリシクロイリシノンを含む痴呆症治療薬

含有三环蓖麻酮的痴呆症治疗