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| 融点 | 92-97 °C (lit.) | | 沸点 | 265-266 °C (lit.) | | 比重(密度) | 1.0111 (estimate) | | 屈折率 | 1.6070 (estimate) | | FEMA | 3019 | SKATOLE | | 闪点 | 132 °C | | 貯蔵温度 | Store below +30°C. | | 溶解性 | Chloroform (Slightly), Methanol (Slightly) | | 酸解離定数(Pka) | 17.30±0.30(Predicted) | | 外見 | Crystalline Powder or Flakes | | 色 | Almost white to pale brown | | 臭い (Odor) | indole-like odor | | 臭気閾値(Odor Threshold) | 0.0000056ppm | | においのタイプ | animal | | 水溶解度 | Soluble in water, Ether, Alcohols, Benzene, Acetone, Chloroform. | | Sensitive | Light Sensitive | | Merck | 14,8560 | | JECFA Number | 1304 | | BRN | 111296 | | 安定性： | Stable, but light-sensistive. Stench! Incompatible with strong oxidizing agents, strong acids, acid ahydrides, acid chlorides. Combustible. | | InChIKey | ZFRKQXVRDFCRJG-UHFFFAOYSA-N | | LogP | 2.60 | | CAS データベース | 83-34-1(CAS DataBase Reference) | | NISTの化学物質情報 | 1H-Indole, 3-methyl-(83-34-1) | | EPAの化学物質情報 | 3-Methylindole (83-34-1) |
| | 3-メチルインドール Usage And Synthesis |
| 外観 | 白色～わずかにうすい褐色, 結晶～結晶性粉末 | | 性質 | スカトールは毒性がある白色結晶です。時間が経過すると、茶色くなります。融点は95°C、沸点は265°Cです。
水に溶けにくく、アルコール、ベンゼン、エーテルには溶けます。フェリシアン化カリウムや硫酸中で、紫色を呈します。
なお、スカトールはインドール環の3位にメチル基を持っているため、3-メチルインドールとも呼ばれます。インドール環とはピロール環とベンゼン環が縮合した構造のことです。
スカトールのモル質量は131.17g/molで、示性式はC8H6NCH3と表されます。
| | 溶解性 | エタノールに可溶, 水に極めて難溶。水に溶けにくく、エタノール、エーテル、クロロホルム、ベンゼンに易溶。 | | 解説 | 3-methylindole．C9H9N(131.18)．インドールの誘導体．排泄物，ビートの根，ニレ科やクスノキ科のある種の木の幹，コールタール中などに存在する．プロピオンアルデヒドフェニルヒドラゾンC2H5CH=NNHC6H5を塩化亜鉛と加熱して合成する．強い悪臭をもつ白色の葉状晶．融点95 ℃，沸点265～266 ℃．d9941.003．熱水，アルコール類，エーテルに可溶．生体内ではトリプトファンからインドール酢酸を経て生成される．LD50 3450 mg/kg(ラット，経口)．森北出版「化学辞典（第2版） | | 解説 | 3-メチルインドールのこと。タール系インドールの高沸点留分や人の排泄物に存在する不快臭をもつ白色葉状晶。融点 95℃。人体ではトリプトファンの分解によって生成する。プロピオンアルデヒドとフェニルヒドラゾンから、塩化亜鉛の存在下で合成される。プロピオンアルデヒドのフェニルヒドラゾンを塩化銅と加熱してつくる。有機溶媒には溶けやすく，松材に対し呈色反応を示す。希薄溶液は芳香をもっているので，花精油の保留剤として用いられる。 | | 用途 | インドールと同様に花精油の変調剤、保留剤として少量用いる。 | | 合成 | 1. スカトールの合成法
フィッシャーのインドール合成 (英: Fischer indole synthesis) によって、スカトールを合成可能です。フィッシャーのインドール合成とは、酸触媒を用いてフェニルヒドラゾンを熱すると、インドールが得られる化学反応のことです。
エミール・フィッシャー (英: Hermann Emil Fischer) によって開発されました。酸触媒として、硫酸や塩酸のほか、三フッ化ホウ素ジエチルエーテル錯体 (BF3・OEt2) やのようなルイス酸も使用されます。
フィッシャーのインドール合成の変法として、O-ビニル-N-フェニルヒドロキシルアミンから合成する手法やO-フェニルオキシムからベンゾフランを得る手法も知られています。
ヤップ・クリンゲマン反応 (英: Japp-Klingemann reaction) を用いて、ジアゾニウム化合物から中間体であるフェニルヒドラゾンの誘導体を合成可能です。
2. スカトール合成のメカニズム
図2. スカトールの合成
フィッシャーのインドール合成ではまず、酸触媒がフェニルヒドラゾンの持つイミノ基の窒素原子に結合します。そしてイミノ基のα位のプロトンが放出されて、フェニルヒドラゾンがエナミン型になります。スカトールの合成で使用するアルデヒドやケトンは、プロピオンアルデヒド (英: propionaldehyde) です。
次に[3,3]-シグマトロピー転位 (英: [3,3]-sigmatropic rearrangement) によって、窒素-窒素結合が開裂し、エナミン部分の炭素原子とベンゼン環上の炭素原子が結合します。イミノ基にベンゼン環上の窒素原子が求核攻撃して、ジアザヘミアセタールを生成し、酸触媒によってアンモニアが脱離すると、インドール環が得られます。 | | 化学的特性 | Skatole has a characteristic putrid, fecal odor at high concentrations, becoming pleasant, jasmine-like, fruity sweet, warm at very low concentrations. It has a warm overripe fruity flavor below 1 ppm. | | 物理的性質 | White crystals or slightly brown platelets. soluble in 3 volumes of 95% ethanol and oily fragrance. 3-Methylindole has a salty and strong indole-like animal fragrance, which is very powerful, has strong diffusion and is very durable. The smell at high concentrations is disgusting, only at very low concentrations there is a large civet-like animal aroma, and the taste is warm and overripe fruit-like. | | 天然物の起源 | Skatole is an indole derivative with a strong fecal odor that occurs naturally in feces formed due to the degradation of tryptophan. It is found in several flowers such as jasmine owing to its flowery smell when present in low concentration. Skatole is also one of the key contributors to the development of boar taint in fat samples.
Reported found in beetroot, feces, coal tar, Swiss cheese, Gruyere cheese, mozarella cheese, butter, milk, goat and sheep milk, boiled egg, fatty fish, coffee, tea, trassi, rice bran, dried bonito and squid. | | 使用 | 3-Methylindole is a naturally abundant pneumotoxin, found primarily in mammalian feces providing its strong fecal odor. In lower concentrations however, the compound has a pleasent aroma, giving orange blossoms and ja smine their pleasing scent. It is often a component of commercial fragrances and perfumes.It helps fluorescent guanosine analogue, which in a dimethoxytrityl, phosphoramidite protected form, can be site-specifically inserted into oligonucleotides through a 3'-5' phosphodiester linkage using an automated DNA synthesizer. | | 製造方法 | Prepared synthetically from the phenylhydrazone of propionaldehyde or by cyclization of o-toluidides (Bedoukian, 1967).
Industrial synthesis of 3-Methylindole: Propionaldehyde phenylhydrazone is obtained by heating propionaldehyde and phenylhydrazine to remove water molecules, and then heating with zinc chloride or sulfuric acid to remove ammonia molecules to obtain 3-Methylindole.
3 Step Synthesis of 3-Methylindole (Skatole) via Hydroboration and Cyclization | | 定義 | ChEBI: 3-Methylindole, or skatole, belongs to the indole family and has a methyl substituent in position 3 of the indole ring. It is produced during the anoxic metabolism of L-tryptophan in the mammalian digestive tract. It has a role as a mammalian metabolite and a human metabolite. | | Aroma threshold values | Detection: 0.2 ppb | | Synthesis Reference(s) | Journal of the American Chemical Society, 99, p. 3532, 1977 DOI: 10.1021/ja00452a073
The Journal of Organic Chemistry, 45, p. 2709, 1980 DOI: 10.1021/jo01301a032
Tetrahedron Letters, 28, p. 5291, 1987 DOI: 10.1016/S0040-4039(00)96710-8 | | 一般的な説明 | 3-Methylindole (3-MI), commonly found in wine, dairy products, and other foodstuffs, leads to an unpleasant fecal like odor in pig meat products. It is reported to be produced in the intestines of several species by the microbial degradation of tryptophan. | | 使用用途 | 低濃度のスカトールは、化粧品調合香料に利用可能です。スカトールは人が嫌う強烈な悪臭ですが、濃度が低いと花のような香りを感じます。
香水の3大フラワー匂いの1つであるジャスミンにもスカトールは含まれており、その香りの中にもかすかに糞尿を感じさせる香りを含んでいます。ただし、多くの人は「甘く柔らかな香り」に感じ、糞尿のような悪臭を感じません。
多くの香水の香料や定着剤のほか、タバコの香料や添加物としても、スカトールを使用可能です。
| | 類似物 | 
図3. スカトールの関連化合物
メチル基を有するインドール誘導体には、スカトール以外にも、1-メチルインドール、2-メチルインドール、4-メチルインドール、5-メチルインドール、6-メチルインドール、7-メチルインドールがあります。2-メチルインドールはメチルケトール (英: methylketol) とも呼ばれます。
| | 薬理学 | Skatole (l00mg dissolved in 2 ml sesame oil administered by gastric intubation)
failed to prevent apoplexy in the adrenals of rats when administered 24 hr before injection of 5 mg
of 7,12-dimethylbenz[a]anthracene (Huggins & Fukunishi, 1964).
In rat costal cartilage, skatole inhibited 35SO42-incorporation into chondroitin sulphate and 14C-labelled proline incorporation into protein (Liberti & Rogers, 1970). In concentrations of 5-10 mM, it inhibited oxygen uptake in slices of rat liver and rat-brain cortex (Lascelles & Taylor, 1968; Walshe et al. 1958). Skatole has also shown depressant (catatonic-like) activity on the swimming behaviour of guppies and the exploratory behaviour of rats (Sprince, 1969). When injected ip, 1 mmol/kg did not have any radioprotective effect in mice, the survival effect (ratio of mean survival time in a treated group to that of the control in 30 days after irradiation) being 0.97
or 0.70 when skatole was administered 30 or 5 min, respectively, before X-irradiation with 800 R
(Shinoda et al 1974).
Skatole (1.0mM) caused >50% inhibition of the anaphylactic release of histamine from chopped,
sensitized guinea-pig lung by chymotrypsin substrates and inhibitors (Austen & Brocklehurst, 1961).
It had a non-specific excitatory action on the heart of the marine mollusc Venus mercenaria (Greenberg,
1960) and in a 194 μM concentration produced half-maximal positive inotropic activity in
isolated left guinea-pig atria (Zetler, 1974). | | 安全性プロファイル | Poison by ingestion,
intravenous, and intraperitoneal routes.
Moderately toxic by subcutaneous route.
When heated to decomposition it emits
toxic fumes of NOx. | | 毒性学 | 3-Methylindole (3MI), an abnormal metabolite of tryptophan, causes acute pulmonary edema and emphysema. 3MI toxicity is species-, tissue- and cell-specific and is an excellent model for understanding the processes of chemically-induced lung injury. This 3-methylindole (3-MI) is absorbed through the rumen wall and circulated around the body. The 3-MI is toxic to the primary cells that line the interior surface of the lungs. Thus, as the high levels of 3-MI move from the rumen to the lungs more and more lung tissue is destroyed.
Toxicity of 3-Methyleneoxindole, a Proposed Reactive Intermediate in the Metabolism of 3-Methylindole
The metabolic basis of 3-methylindole-induced pneumotoxicity
Association of 3-methyleneindolenine, a toxic metabolite of 3-methylindole, with acute interstitial pneumonia in feedlot cattle
Mechanisms of 3-methylindole pneumotoxicity | | 合成 | Indoles (skatole) with various substituents in the 2 and 3 position can be synthesized via the Fisher indole synthesis, which involves two steps and utilizes a phenylhydrazine and an aliphatic or aromatic aldehyde or ketone as starting materials. | | 代謝経路 | Three major metabolites of 14C-skatole are found in
the plasma/urine of pigs given skatole and are
identified as 6-sulfatoxyskatole, 3-hydroxy-3-
methyloxindole, and the mercapturate adduct of
skatole, 3-[(N-acetylcysteine-S-yl)methyl]indole. For
other pathways, see the references in the text. | | 代謝 | 3-Methylindole (skatole) has been reported by several authors to be excreted as an ethereal sulphate by dogs, rats and man; distillation of the urine results in the formation of indole, which might well be derived by decarboxylation of indolyl-3-carboxylic acid, an expected oxidation product of skatole (Williams, 1959). Oral administration of skatole to rats resulted in the urinary excretion of a mixture of sulphate esters of hydroxyskatoles (Dalgliesh, Kelly & Horning, 1958; Horning, Sweeley, Dalgliesh & Kelly, 1959). The faeces of rats fed a chow diet were found to contain typtophan metabolites, including up to 0.78 ?g skatole/g wet faeces (Anderson, 1975). Metabolites of skatole were detected in the urine of a human subject fed skatole (Sano & Miyanoki, 1955). In man, skatole has been shown to undergo hydroxylation mainly at position 6. In rats and man, 6-hydroxyskatole is excreted chiefly as the sulphate (Horning et al. 1959), but it may also be excreted as the glucuronide (Sohler, 1966). The metabolites of skatole excreted in the urine of man and 16 species of domestic and wild mammals were also studied by Decker & Gerdemann (1959). After administration of skatole to cattle in a dose of 0.1-0.2 g skatole/kg intraruminally or 0.06g/kg by jugular infusion, the mean plasma concentration of skatole became maximal at 3 and 9hr, respectively (Carlson et al. 1975). | | 純化方法 | Crystallise skatole from *benzene or pet ether (m 96.5o). It has also been purified by zone melting. The picrate has m 182o (from Et2O or Et2O/MeOH). [Beilstein 20 III/IV 3206, 20/7 V 69.] |
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