DEVELOPMENT OF POTENT ACTIVE COMPOUNDS WORKING ON NEUROTRANSMIT ORGAN
开发作用于神经传递器官的有效活性化合物
基本信息
- 批准号:04554021
- 负责人:
- 金额:$ 3.97万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Developmental Scientific Research (B)
- 财政年份:1992
- 资助国家:日本
- 起止时间:1992 至 1993
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Among neurocells signals are transmitted by compounds called neurotransmitters. Glutamic acid is one of them and it is released from a fore-cell are and received by a receptor of a back-cell. This glutamate receptor is believed to play a role in the important functions such as memory and learning. Studies on the function of the receptor through organic synthesis have been achieved in this project.1) Acromelic acid B was synthesized in 21% orverall yield. It was acomplished by the intramolecular Diels-Alder addition of a enolate of an aromatic aldehyde formed by the irradiation of UV light to a doulbe bond conjugated to ester.2) Conformational analysis of L-2-(carboxycyclopropyl)glycine (CCG) was carried out. CCGs would be a probe to clear the conformational demand of the glutamate receptor to the substrate. Several 3'-substituted CCG analogues were synthesized and observed their biological activities and their conformational analysis were carried out spectroscopically. Spatial arrangem … More ent of the functional groups in the substrate was consequently recognized and new agonists were also developed.3) The conformational demand for the pi-electron plane of the C_4 side-chain of kainoid was investigated. X-ray and spectroscopic studies on the strongly active kainoids show the diagonal arrangement of the pi-electron plane and pyrrolidine ring. The compounds whose pi-electron plane has almost the same plane as pyrrolidine ring were synthesized this time. They are 3-aza-2, 8-dicarboxy-6-methylbicyclo[3.3.0] octane system containing a double bond around C_6 in exo or end positions. All of their biological activities depressed very much and it shows that the diagonal relationship between the pi-electron plane and pyrrolidine ring is required to show strong biological activity.4) A short step synthesis of aromatic kainoid was newly developed. It depends on the addition of a radical species generated from methyl malonate by oxidation with Mn(III) to 4-aryl-3-dehydroproline. The lactone from of 4-aryl-2-carboxymethyl-4-hydroxyproline was first produced and it was converted to arylkainoid through hydrogenolysis of C_4-hydroxyl group.5) Four stereoisomers of 2-carboxy-4-methylenecyclopentylglycine (CPG) were synthesized by the addtion of trimethylenemethane to 3-dehydroglutamic acid. Among them, only CPG-IV was biologically active as potent as kainic acid. Less
在神经细胞之间,信号是由一种叫做神经递质的化合物传递的。谷氨酸就是其中之一,它从前细胞释放出来,并被后细胞的受体接收。这种谷氨酸受体被认为在记忆和学习等重要功能中发挥作用。本课题通过有机合成的方法对该受体的功能进行了研究。1)以21%的总收率合成了苯丙酸B。通过分子内Diels-Alder加成反应,将紫外光照射下形成的芳香醛的烯酸酯加成到与酯相连的双键上。2)对L-2-(羧基环丙基)甘氨酸(CCG)进行了构象分析。CCGs可以作为一种探针,清除谷氨酸受体对底物的构象需求。合成了几个3‘取代的CCG类似物,观察了它们的生物活性,并对它们的构象进行了光谱分析。空间排列…3)研究了红藻氨酸C_4侧链pi电子平面的构象需求。对强活性红藻氨酸的X-射线和光谱研究表明,pi电子平面和吡咯烷环呈对角排列。合成了与吡咯烷环具有几乎相同平面的电子平面的化合物。它们是3-氮杂-2,8-二羧基-6-甲基双环[3.3.0]辛烷体系,在C6的外位或末端含有一个双键。所有化合物的生物活性都受到了很大程度的抑制,这说明芳香海人藻类化合物的合成需要pi电子平面与吡咯烷环之间的对角关系才能表现出较强的生物活性。4)新开发了一种短步合成芳香海藻碱化合物的方法。它依赖于由丙二酸甲酯与Mn(III)氧化生成的自由基物种的加成反应。首先合成了4-芳基-2-羧甲基-4-羟基丙氨酸的内酯,然后通过C_4-羟基的氢解将其转化为芳基海藻酸。5)通过三亚甲基甲烷与3-脱氢谷氨酸的加成反应合成了4个2-羧基-4-亚甲基环戊基甘氨酸(CPG)的立体异构体。其中,只有CpG-IV具有与红藻氨酸一样的生物活性。较少
项目成果
期刊论文数量(114)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
K.Yamano: "Isolation of L-N-[2-(3-Pyridyl)ethyl]-glutamic Acid from the Poisonous Mushroom Clitocybe acromelalga.A Possible Intermediate in the Biogenesis of Acromelic Acids" Chem.Lett.34. 21-24 (1993)
K.Yamano:“从有毒蘑菇 Clitocybe acromelalga 中分离 L-N-[2-(3-吡啶基)乙基]-谷氨酸。Acromelic Acids 生物合成中可能的中间体”Chem.Lett.34。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
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- 通讯作者:
M.Ishida: "A novel metabotropic glutamate agonist:marked depression of monosynaptic excitation in the isolated newborn rat spinal cord" Bioorg.Med.Chem.Lett.109. 1169-1177 (1993)
M.Ishida:“一种新型代谢型谷氨酸激动剂:分离的新生大鼠脊髓中单突触兴奋的显着抑制”Bioorg.Med.Chem.Lett.109。
- DOI:
- 发表时间:
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- 影响因子:0
- 作者:
- 通讯作者:
S.Raghavan: "Synthesis of 2-(2-carboxy-4-methylenecyclopentyl)glycines(CPFGs).Novel conformationally restricted glutamate analogues" Tetrahedron Lett.36. 5765-5768 (1993)
S.Raghavan:“2-(2-羧基-4-亚甲基环戊基)甘氨酸(CPFG)的合成。新型构象限制的谷氨酸类似物”四面体快报.36。
- DOI:
- 发表时间:
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- 影响因子:0
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篠崎 温彦: "新しい興奮性アミノ酸受容体アゴニストの基礎的研究" てんかん治療研究振興財団研究年報. 5. 26-33 (1993)
Atsuhiko Shinozaki:“新型兴奋性氨基酸受体激动剂的基础研究”癫痫治疗研究基金会年度报告 5. 26-33 (1993)。
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- 影响因子:0
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N.Sakai: "Total Synthesis of Galantin I.Acid-Catalyzed Cyclination of Galantinic Acid" J.Am.Chem.Soc.114. 998-1010 (1992)
N.Sakai:“加兰汀 I 的全合成。酸催化加兰汀酸的环化”J.Am.Chem.Soc.114。
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- 影响因子:0
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SHIRAHAMA Haruhisa其他文献
SHIRAHAMA Haruhisa的其他文献
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{{ truncateString('SHIRAHAMA Haruhisa', 18)}}的其他基金
Structure Determination, Synthesis and Biological Activity of Neuroactive Compounds
神经活性化合物的结构测定、合成及生物活性
- 批准号:
07458145 - 财政年份:1995
- 资助金额:
$ 3.97万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
ORGANIC CHEMISTRY OF THE BIOSYSTEM CONTROL SUBSTANCES
生物系统控制物质的有机化学
- 批准号:
03303003 - 财政年份:1991
- 资助金额:
$ 3.97万 - 项目类别:
Grant-in-Aid for Co-operative Research (A)
Isolation, Structural Determination and Synthesis of Biologically Active Substances Produced by Fungi
真菌产生的生物活性物质的分离、结构测定和合成
- 批准号:
63430007 - 财政年份:1988
- 资助金额:
$ 3.97万 - 项目类别:
Grant-in-Aid for General Scientific Research (A)
Studies on the inhibitors from plant pathogens produced by soil germs
土壤病菌产生的植物病原菌抑制剂的研究
- 批准号:
62840017 - 财政年份:1987
- 资助金额:
$ 3.97万 - 项目类别:
Grant-in-Aid for Developmental Scientific Research
Synthesis of accromelic acids and their derivatives
丙烯二酸及其衍生物的合成
- 批准号:
61470029 - 财政年份:1986
- 资助金额:
$ 3.97万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
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