著者
犀川 陽子 岡本 博樹 乾 泰地 橋本 貴美子 中田 雅也 真壁 みどり 奥野 智旦 須田 隆
出版者
天然有機化合物討論会
雑誌
天然有機化合物討論会講演要旨集
巻号頁・発行日
no.43, pp.443-448, 2001-09-01

A poisonous mushroom Podostoma cormu-damae caused two lethal poisoning in Japan in 1999 and 2000. Some of the following symptoms are observed in these poisonings: gastrointestinal disorder, erroneous perception, decrease in the number of leukocytes and thrombocytes, deciduous skin of face, loss of hair, and atrophy of the cerebellum which brings about a speech impediment and voluntary movement problems. We studied the toxic constituents of its culture broth and the fruit bodies using lethal effect on mice as an index. The extracts from the culture filtrate and the fruit bodies were injected into the abdominal cavity of a mouse. The lethal effect was observed in both extracts from the culture filtrate and the fruit bodies. The organic extracts of the culture filtrate were chromatographed on silica gel to give the major compounds 1, 2, and 3. The ^1H and ^<13>C NMR spectroscopic analyses revealed that these compounds 1〜3 are members of the macrocyclic trichothecene group. Comparison of the spectral data of 1〜3 with those in the literature revealed that 1 is roridin E, 2 is verrucarin J (muconomycin B), and 3 is satratoxin H. On the other hand, the fruit bodies were extracted with water and methanol. The water extracts were chromatographed on ODS to give satratoxin H (3), and the methanol extracts were chromatographed on silica gel to give 4〜6. The NMR and MS analyses showed that 4, 5, and 6 is the 12',13'-diacetate, 12'-acetate, and 13'-acetate of satratoxin H (3), respectively. The 4〜6 are new compounds that occur in nature. All these macrocyclic trichothecenes except for 2 had a lethal effect on mice by at least 0.5 mg per capita.
著者
犀川 陽子
出版者
慶應義塾大学
雑誌
新学術領域研究(研究領域提案型)
巻号頁・発行日
2012-04-01 (Released:2013-05-15)

非アレルギー性くしゃみ反射を誘発する天然有機化合物に注目し、くしゃみ誘発活性の定量法を確立して新たな化合物の探索および既知のくしゃみ誘発物質の構造活性相関を調べる研究を行った。くしゃみ誘発活性試験法として、定期的にオブアルブミンを投与することで鼻アレルギーマウスモデルを作成し、その鼻孔に試料を塗布してくしゃみの数を数える方法を採用した。アレルギー状態の減衰やマウスの個体差の補正のためにポジティブコントロールを並行して用いることで、くしゃみ誘発活性の定量法を確立した。アカクラゲ由来のくしゃみ誘発物質の探索:ハクションクラゲの別名を持つアカクラゲから、くしゃみ誘発物質を単離、構造決定する目的で研究を行った。これまでにアカクラゲからくしゃみを誘発する化合物として3種の不飽和脂肪酸を同定したが、今回改めて抽出方法の検討から行った。その結果、アカクラゲの触手の乾燥粉を水にて抽出した溶液には、時間経過と共に活性の減衰するくしゃみ誘発物質が存在することがわかり、これを短時間で精製を試みた結果、活性本体はタンパク性の刺胞毒である可能性を示唆する実験結果が得られた。グラヤノトキシン類の構造とくしゃみ誘発活性との相関に関する研究:くしゃみを誘発することが知られているグラヤノトキシン類をハナヒリノキやアセビから抽出、化学誘導し、14種類の類縁体を得た。これらのくしゃみ誘発活性の定量を行った結果、グラヤノトキシンIが最も強いくしゃみ誘発活性を示し、その異性体では全く活性を示さないことが明らかとなり、分子構造のわずかな違いを正確に見分けるくしゃみ受容体の存在が示唆された。試験したグラヤノトキシン類のくしゃみ誘発活性と構造の相関は毒性やナトリウムイオンチャネル開口活性と構造の相関に近いことがわかり、ナトリウムイオンチャネルへの作用がくしゃみ誘発に関わると予想している。
著者
松浦 正憲 加藤 優 犀川 陽子 乾 公正 橋本 貴美子 中田 雅也
出版者
天然有機化合物討論会
雑誌
天然有機化合物討論会講演要旨集
巻号頁・発行日
no.50, pp.415-420, 2008-09-01

Accidental ingestion of a toadstool, Russula subnigricans causes lethal poisoning to human. In the 1950's, the first poisoning caused by this mushroom was reported. Since then there have been no reports about lethal poisoning for 50 years, which was enough to raise doubts about its existence. However, in these three years, 2005 to 2007, the poisoning accidents were continuously happened and four people died. Although chemical studies on this fungus were reported using mushrooms distributed in Miyagi prefecture, the isolated compounds, russuphelins, russupherol, and hydroxybaikiain, have no toxicity on mouse. Accordingly, we studied the isolation of the toxic constituent of R. subnigricans. One of the reasons that such a strong toxin has not been revealed until now is the incomplete classification of this mushroom, that is, there are many resemble species distributed in Japan. We collected three species in Kyoto, Miyagi, and Saitama prefectures. The aforementioned compounds were found only in the Miyagi species. All three species show toxicity on mouse by intraperitoneal injection of the water extract; however, only the Kyoto species exhibits toxicity by oral injection. Accordingly, we estimated that the Kyoto species is the genuine R. subnigricans. During the separation steps, we found that the toxicity was remarkably decreased after concentration to dryness; therefore, all manipulations were carefully performed. The water extract was successively separated through ODS column chromatography, ion exchange chromatography, and gel filtration to give an aqueous solution of the toxic compound. The toxic compound was revealed to be unstable under concentration to dryness (polymerization occurs) and volatile, which was turned out to be the cause of decrease in toxicity after evaporation. The unstable toxin was converted to a stable derivative using diphenyldiazomethane. Taking ^1H, ^<13>C NMR and MS spectral analyses of the toxic compound and its derivative into consideration, the structure of the toxic compound was determined to be cycloprop-2-ene carboxylic acid. This compound was found only in the Kyoto species.
著者
犀川 陽子
出版者
慶應義塾大学
雑誌
若手研究(B)
巻号頁・発行日
2007 (Released:2007-04-01)

ミドリイガイの殻皮層を塩酸抽出したのちイオン交換、分子ふるい、逆相クロマトグラフィーなどを用いて精製を行い、主成分である青色色素が光、酸素に安定で親水性の色素ペプチドであることを明らかにした。また、アカクラゲ由来の刺激物質の探索を敏感マウスのくしゃみを用いた評価法にて行った。抽出物のヘキサン画分をシリカゲルや逆相クロマドグラフィーにて精製し、有意な活性を持つ脂肪酸を分離した。