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
• 负责人: SHIRAHAMA Haruhisa
• 金额: $ 20.61万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63430007/
• 关键词: Clito eybe acromeralga; New kainoid; New synthetic method of kainoids; neuroexcitatory substonces; Gymnopilus spectalilis; Gymnopolin; Suillus greevillei; Lipid peroxilation inhibitor; 神経毒; 過酸化脂質生成阻害; 担子菌; 過酸化脂質生成阻害活性; アクロメリン酸; カイノイド; 神経興奮性ア

1. Dokusasako (a poisonous mushroom)-neuroexcitatory amino acids and their chemical development. Clitidine, clithioneine, acromelic acids A and B, and 4-amino quinolinic acid were isolated from the mushroom but other new poisonous principles must be contained in this fungus. We have tried to isolate them and a new amino acid and a new fraction acting as a neuroexcitant have been found. The structure of the new amino acid was deduced from spectroscopic data and its biogenesis and confirmed by the synthesis. 4-(2-Carboxypyrrolyl)-3-alanine was synthesized from 4-formylpyrrol-2- carboxylic acid ester and found to be identical with the new natural amino acid. The synthetic compound was optically resolved with a chiral plate and their CD were measured. Rf value on the chiral plate and CD sign of the natural product was coincided with synthetic L-acid. A new neuroexcitatory fraction was also found and undergoing its structural studies now. As the acromelic acids were recognized as a tool of … More neuropharmacological studies, so many requests for supplying the reagents were received. Design of the reagent which is so active as the acromelic acids and more easily accessible and development of the synthetic method of such reagents have been studied. The highly stereoselective construction of pyrrolidine ring with C4 substituent by a photo-induced Diels-Alder reaction was successfully carried out to give a new methoxyphenyl kainoid which was stronger neuroexcitant than acromelic acid itself. Furthermore, stereoselective substitution reaction of tosylate group on the C4 position of proline was smoothly performed and the easier general procedure for various kainoid was established. 2. Ohwaraitake (a poisonous mushroom)-a neuroexcitant and stereochemistry of gymnopilin. A previously isolated bitter principle gymnopilin A10 and/or All is probably new neuroexcitants. We sought for neuroexcitatory constituents in this toadstool testing depolarizing activity of a rat spinal cord and reached to the above conclusion. It is very rare and interesting that such a chain origoisoprenoid alcohol shows neuroexcitatory activity. Stereochemistry 6 or 7 quarternary carbon or the gymnopilin was under investigation by synthesis. 3. Hanaiguchi (an eddible mushroom)-a lipid peroxidation inhibitor. The title compound was isolated from the mushroom and its structure was determined as 1-acetoxy-2-geranylgeranyl-4, 6-dihydroxybenzene by spectral studies. Less

1.毒蘑菇-神经兴奋性氨基酸及其化学发展。从该菌中分离出了Clitidine、Clithioneine、acromelic acids A和B以及4-氨基喹啉酸，但该菌还可能含有其它新的有毒成分。我们尝试分离它们，发现了一个新的氨基酸和一个新的神经兴奋剂组分，根据光谱数据和生物来源推测了新氨基酸的结构，并通过合成证实了新氨基酸的结构。以4-甲酰基吡咯-2-羧酸酯为原料，合成了4-（2-羧基吡咯基）-3-丙氨酸，并与新的天然氨基酸进行了结构鉴定。用手性板对合成的化合物进行了光学拆分，并测量了它们的CD。天然产物的手性板上的Rf值和CD符号与合成的L-酸一致。另外，还发现了一个新的神经兴奋组分，目前正在对其进行结构研究。由于丙烯酸被认为是一种工具， ...更多信息 由于神经药理学研究的需要，收到了许多提供试剂的请求。研究了既具有丙烯酸类化合物的活性又易于获得的试剂的设计和合成方法的发展。通过光诱导Diels-Alder反应，高立体选择性地合成了一种新的甲氧苯基红藻氨酸类化合物，该化合物的神经兴奋性比丙烯酸强。此外，脯氨酸C4位上的甲苯磺酸酯基团的立体选择性取代反应顺利进行，并建立了各种红藻氨酸的更容易的通用程序。2.大原香菇（一种有毒的蘑菇）-一种神经兴奋剂和裸毛素的立体化学。先前分离的苦味成分裸毛素A10和/或All可能是新的神经兴奋剂。我们通过对大鼠脊髓的去极化实验，寻找毒蕈中的神经兴奋成分，并得出上述结论。这是非常罕见和有趣的，这样一个链origoisoprenoid醇显示神经兴奋活动。立体化学6或7季碳或gymnopilin正在研究中的合成。3.花旗参（一种食用菌）-脂质过氧化抑制剂。标题化合物从蘑菇中分离得到，经波谱分析确定其结构为1-乙酰氧基-2-香叶基香叶基-4，6-二羟基苯。少

项目成果

K. Hashimoto, et al.: "Synthesis of New Acromelic Acid Congeners : Novel Neuroexcitatory Amino Acids Acting on Glutamate Receptor." Tetrahedron Lett.32. (1991)

K. Hashimoto 等人：“新 Acromelic Acid 同系物的合成：作用于谷氨酸受体的新型神经兴奋性氨基酸。”

H.Shirahama: "Synthesis and Neuroexcitatory Activity of Pyrrolidineー2,3ーDicarboxylic Acids(PRDA):Conformationally Constrained LーAsp Derivatives" Tetrahedron Lett.32. (1991)

H. Shirahama：“吡咯烷-2,3-二羧酸 (PRDA) 的合成和神经兴奋活性：构象约束的 L-Asp 衍生物”Tetrahedron Lett.32。

H.Shirahama;K.Konno;K.Hashimoto;T.Matsumoto: "Neurotox'88 Molecular Basis of Drug ＆ Pesticide Action Chater 9" Excerpta Medica,Elsevier Science Publishers, 105-122 (1988)

H.Shirahama;K.Konno;K.Hashimoto;T.Matsumoto：“Neurotox88 药物和农药作用的分子基础 Chater 9”医学摘录，Elsevier Science Publishers，105-122 (1988)

柳田 美和: "Syntheses of Acyclic Analogues of Kainoids and Neuroexcitatosy Activity" Tetrahedron Letters. 30. 3799-3802 (1989)

Miwa Yanagida：“凯诺类无环类似物和神经兴奋活性的合成”四面体快报 30。 3799-3802 (1989)

紺野 勝弘: "Acromelic Acids A and B.Potent Excitatory Amino Acids gsolated from Clitocybe acromelalga" Journal of American Chemicol Society. 110. 4807-4815 (1988)

Katsuhiro Konno：“从 Clitocybe acromelalga 中提取的强效兴奋性氨基酸 Acromelic Acids A 和 B”，《美国化学学会杂志》110。4807-4815 (1988)。