流涎胺 | 20084-93-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚里西啶
• 中文名称: 流涎胺
• 英文名称: (1S,6S,8aS)-1-acetoxy-6-aminooctahydroindolizidine
• 英文别名: (1S,6S,8aS)-6-aminooctahydroindolizin-1-yl acetate；(-)-Slaframine；slaframine；[(1S,6S,8aS)-6-amino-1,2,3,5,6,7,8,8a-octahydroindolizin-1-yl] acetate
• CAS: 20084-93-9
• 化学式: C₁₀H₁₈N₂O₂
• 分子量: 198.265
• InChiKey: YYIUHLPAZILPSG-GUBZILKMSA-N

物化性质

• 沸点：
  278.5±35.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

Slaframine被认为在肝脏中被一种肝微粒体黄素蛋白氧化酶激活，转化为一种与副交感神经递质乙酰胆碱结构相似的酮亚胺代谢物。

Slaframine is though to be activated in the liver by a hepatic microsomal flavoprotein oxidase to a ketoimine metabolite with a configuration similar to that of the parasympathetic neurotransmitter acetylcholine. (A3092)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

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Slaframine is a parasympathomimetic compound and causes increased secretion by salivary glands, pancreas, and other exocrine and endocrine glands. This is due to its activity as a cholingergic agonist. Slaframine has a high affinity for muscarinic receptors, especially in the gastrointestinal tract, and it stimulates these to produce its parasympathomimetic effects. Slaframine is also known to affect the concentration of circulating metabolic hormones, though the mechanism of this is unknown. (A3091, A3092)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

Slaframine是一种拟副交感神经化合物，会导致外分泌功能增加，尤其是唾液分泌。与另一种生物活性化合物、相思豆菌产生的生物碱相思豆碱一起，它会导致家畜摄入受污染的饲料后出现一种称为“流涎综合症”的状况。（A3091, A3092）

Slaframine is a parasympathomimetic compound and causes increased exocrine function, especially salivation. Along with swainsonine, the other biologially active compound of R. leguminicola, it is known to cause a condition called "slobbers syndrome" in livestock that has ingested contaminated feed. (A3091, A3092)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

口服、皮肤、吸入和 parenteral（被污染的药物）。 (A3101)

Oral, dermal, inhalation, and parenteral (contaminated drugs). (A3101)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

“流涎综合症”的主要症状是大量流涎。其他症状包括腹泻、流泪、关节僵硬、频繁排尿、颤抖、自然流产、呼吸困难、食欲不振、膨胀，甚至可能死亡。

The major symptom of "slobbers syndrome" is profuse salivation. Other symptoms include diarrhea, lacrimation, stiff joints, frequent urination, tremors, spontaneous abortion, labored breathing, loss of appetite, bloat, and possibly death. (A3092)

来源:Toxin and Toxin Target Database (T3DB)

反应信息

• 作为反应物：
  描述：

  乙酸酐 、 流涎胺 在 吡啶 作用下， 以87%的产率得到(1S,6S,8aS)-1-acetoxy-6-(N-acetylamino)-1,2,3,5,6,7,8,8a-octahydroindolizin
  参考文献：
  名称：

  Enantioselective Allyltitanation. Synthesis of (-)-Slaframine

  摘要：

  报告了从醛 1 对吲哚利嗪生物碱 (-)-slaframine 的对映选择性合成。通过对映选择性烯丙基钛化和 Mitsunobu 反应引入了 C-1 和 C-8a 的立体中心。无环化合物 (-)-10 的还原双环化反应生成了 (-)-slaframine 的双环骨架。

  DOI：

  10.1055/s-2002-28505
• 作为产物：
  描述：

  (S)-n-苄基谷氨酸 在 palladium on activated charcoal 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 硼烷四氢呋喃络合物 、 草酰氯 、 二苯基膦叠氮化物 、 四丁基氟化铵 、 氢气 、 碳酸氢钠 、 potassium carbonate 、 二甲基亚砜 、 三乙胺 、 间氯过氧苯甲酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 169.5h， 生成 流涎胺
  参考文献：
  名称：

  Synthesis of (-)-slaframine and related indolizidines

  摘要：

  An enantioselective synthesis of the indolizidine alkaloid (-)-slaframine 1 is reported. Reductive double cyclization of the azido epoxy tosylate 48 afforded the indolizidine 52, which was converted to (-)-slaframine in two steps. The cyclization substrate 48 was prepared in optically pure form from L-glutamic acid. A similar sequence starting with the epoxide 49 allowed the synthesis of (-)-1,8a-diepislaframine 56. Other routes to slaframine were investigated, often using an intramolecular cycloaddition of an azide with an alkene as a key step. Although these routes did not produce slaframine, they illustrated novel and efficient methods for the assembly of the indolizidine skeleton. Cyclization of the azidodiene 20 afforded the indolizidine 21 in one step as a single diastereomer, presumably a result of a chairlike transition state in the initial dipolar cycloaddition. Desulfurization and deprotection produced (-)-8a-epidesacetoxyslaframine 27. Cyclopropylimine rearrangement of 30 gave the indolizidine 31, which was also converted into (-)-8a-epidesacetoxyslaframine 27. Dipolar cycloaddition of 38 gave the 1-pyrroline 39, which was converted to the indolizidine 40 in one operation using Evans' double alkylation of the 1-metalloenamine derivative of 40. Attempted oxidation of 40 to the ketone 41 was unsuccessful, precluding a reductive amination approach to slaframine.

  DOI：

  10.1021/jo00040a045

文献信息

• Enantiopure <i>N</i>-Acyldihydropyridones as Synthetic Intermediates:  Asymmetric Synthesis of (−)-Slaframine
  作者：Daniel L. Comins、Alan B. Fulp

  DOI：10.1021/ol991083v

  日期：1999.12.1

  [formula: see text] An asymmetric synthesis of (-)-slaframine and N-acetylslaframine has been accomplished starting from an enantiopure dihydropyridone building block. The oxygen-carbon bond at C-1 was incorporated with complete stereoselectivity by using an efficient phenylselenocyclocarbamation reaction.

  从对映体纯的二氢吡啶酮结构单元开始已经完成了（-）-slaframine和N-乙酰基slaframine的不对称合成。通过使用有效的苯基硒代杂环氨基甲酸酯化反应，可以完全立体选择性地结合C-1处的氧碳键。
• ENZYMATIC SYNTHESIS OF ENANTIOMERICALLY ENRICHED DERIVATIVES OF CIS- AND TRANS-CYCLOPENTANE-1,2-DIAMINES
  申请人：EntreChem, S.L.

  公开号：EP2319825A1

  公开（公告）日：2011-05-11

  SUMMARY The present invention relates to the enzymatic resolution of cis-and trans-cyclopentane-1,2-diamine derivatives to obtain enantiomerically pure or enriched compounds, a method for the preparation of the starting materials of that procedure, the products of this procedure and its transformation into products of commercial interest.

  摘要 本发明涉及酶解顺式和反式环戊烷-1,2-二胺衍生物以获得对映体纯度或富集度高的化合物、制备该过程起始材料的方法、该过程的产物及其转化为具有商业价值的产品。
• Radical routes to indolizidines. Synthesis of (-)-slaframine
  作者：Spencer Knapp、Frank S. Gibson

  DOI：10.1021/jo00044a011

  日期：1992.8

  The synthesis of (-)-slaframine (5) was executed in 11 steps and 25% overall yield from resolved 3(S)-hydroxy-4-pentenamide (22). Two cyclization reactions were used to form the indolizidine skeleton and also to provide the necessary stereocontrol at C-8a and C-6 of the natural product. "Iodolactamization" of 22 gave selectively the cis-pyrrolidinone 21. Later in the synthesis, a silane-mediated radical cyclization of the phenylseleno lactam 33 gave selectively the 6-alpha-hydroxyindolizidinone 35a, an event predictable from model studies-such as 14c --> 15c. Replacement of hydroxy with azido and reduction of the lactam carbonyl gave "slaframine azide", 38, a stable and easily convertible immediate precursor to 5.
• SYNTHETIC MYCOTOXIN ADSORBENTS AND METHODS OF MAKING AND UTILIZING THE SAME
  申请人：Alltech, Inc.

  公开号：EP2470894B1

  公开（公告）日：2021-12-29
• Regioselective Transformation of Malic Acid: A Practical Method for the Construction of Enantiomerically Pure Indolizidines
  作者：Peter Gmeiner、Dagmar Junge

  DOI：10.1021/jo00117a052

  日期：1995.6