鱼尼汀 | 15662-33-6

• 物质功能分类: 天然产物 - 生物碱
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: 鱼尼汀
• 中文别名: 9,21-脱氢-兰尼定；利阿渃定；鱼尼汀[含量＞30%]；利阿诺定
• 英文名称: ryanodine
• 英文别名: [3H]-ryanodine；ryanodine 24；SML1106；(6S)-7c-isopropyl-3t,6a,9-trimethyl-8c-(pyrrole-2-carbonyloxy)-hexahydro-6r,9c-methano-benzo[1,2]pentaleno[1,6-bc]furan-4c,6,7t,8a,8b,9at-hexaol；(6S)-7c-Isopropyl-3t,6a,9-trimethyl-8c-(pyrrol-2-carbonyloxy)-hexahydro-6r,9c-methano-benzo[1,2]pentaleno[1,6-bc]furan-4c,6,7t,8a,8b,9at-hexaol；Ryania；[(1R,2R,3S,6S,7S,9S,10S,11S,12R,13S,14R)-2,6,9,11,13,14-hexahydroxy-3,7,10-trimethyl-11-propan-2-yl-15-oxapentacyclo[7.5.1.01,6.07,13.010,14]pentadecan-12-yl] 1H-pyrrole-2-carboxylate
• CAS: 15662-33-6
• 化学式: C₂₅H₃₅NO₉
• 分子量: 493.554
• InChiKey: JJSYXNQGLHBRRK-YSOSZROBSA-N

物化性质

• 比旋光度：
  D25 +26° (methanol)
• 沸点：
  586.95°C (rough estimate)
• 密度：
  1.2805 (rough estimate)
• 溶解度：
  DMSO：可溶10mg/mL，澄清
• 熔点：
  219-220 °C

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  173
• 氢给体数：
  7
• 氢受体数：
  9

ADMET

毒理性

• 毒性总结

瑞诺定对开放形式的瑞诺定受体具有极高的亲和力，这是一组存在于骨骼肌、平滑肌和心肌细胞中的钙通道。它以如此高的亲和力与受体结合，因此被用作该类离子通道首次纯化的标记，并因此得名。在纳摩尔浓度下，瑞诺定使受体保持半开放状态，而在微摩尔浓度下则完全关闭它们。纳摩尔级结合的效果是，瑞诺定导致钙从细胞质中的肌浆网等钙储存处释放，导致大量肌肉收缩。（维基百科）

Ryanodine has extremely high affinity to the open-form ryanodine receptor, a group of calcium channels found in skeletal muscle, smooth muscle, and heart muscle cells. It binds with such high affinity to the receptor that it was used as a label for the first purification of that class of ion channels and gave its name to it. At nanomolar concentrations, ryanodine locks the receptor in a half-open state, whereas it fully closes them at micromolarconcentration. The effect of the nanomolar-level binding is that ryanodine causes release of calcium from calcium stores as thesarcoplasmic reticulum in the cytoplasm, leading to massive muscular contractions. (Wikipedia)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

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

来源:Toxin and Toxin Target Database (T3DB)

安全信息

• 危险品标志：
  Xn,N
• 安全说明：
  S36/37,S60,S61
• 危险类别码：
  R21/22
• 危险品运输编号：
  UN 3077 9
• RTECS号：
  VM4025000

制备方法与用途

生物活性

Ryanodine 是一种可渗透细胞的兰尼碱受体调节剂。根据其浓度，Ryanodine 可以刺激或抑制 Ryanodine 介导的 Ca2+ 释放。在 Ryania speciosa 中发现了这种有毒二萜。

靶点

• Ryanodine receptor

体内研究

• Ryanodine (100-5000 nM, 30-120 分钟) 以剂量相关的方式不可逆地抑制快肌和慢肌的单收缩及 tetanic 张力。
• 在浓度超过 250 nM 时，Ryanodine 会诱导一种缓慢发展的、剂量依赖性的收缩，这种收缩无法被 5 mM Co2+ 阻断。

类别

农药

毒性分级

中毒

急性毒性

• 口服 - 大鼠 LD50: 750 毫克/公斤；
• 口服 - 小鼠 LD50: 650 毫克/公斤

可燃性危险特性

燃烧产生有毒氮氧化物气体

储运特性

库房通风、低温干燥；与食品原料分开储运

灭火剂

干粉、泡沫、砂土

反应信息

• 作为反应物：
  描述：

  鱼尼汀 在 aluminum oxide 、 苯 Saline 作用下， 生成 3-O-prolinylryanodol
  参考文献：
  名称：

  Ryanoids 和相关化合物 ?? α-吡咯羧酸烷基酯的化学选择性电催化加氢：兰尼碱的选择性加氢

  摘要：

  介绍了吡咯和不同烷基吡咯-2-羧酸盐的电催化加氢 (ECH) 过程的研究。一旦氢化，吡咯-2-羧酸烷基酯变成脯氨酸的酯，脯氨酸是一种重要的天然氨基酸。该过程对吡咯环具有化学选择性。Ryanodine 是一种已知具有生物活性的天然 ryanoid。如此获得的四氢兰尼定衍生物现在可以代表具有高度生物学意义的分子。兰尼碱的氢化可以通过电催化和催化过程进行。在这两种情况下，反应都不是非对映选择性的。关键词：电催化加氢，脯氨酸酯，兰尼丁，四氢兰尼丁。

  DOI：

  10.1139/v02-182
• 作为产物：
  描述：

  9,21-二氢-鱼尼丁-3-(1H-吡咯-2-羧酸) 在 palladium on activated charcoal 氢气 作用下， 以 水 为溶剂， 反应 1.0h， 以3%的产率得到鱼尼汀
  参考文献：
  名称：

  Waterhouse, Andrew L.; Holden, Ian; Casida, John E., Journal of the Chemical Society. Perkin transactions II, 1985, p. 1011 - 1016

  摘要：

  DOI：

文献信息

• Ryanoids and related compounds — Isolation and characterization of 11 new minor ryanoids from the plant<i>Ryania Speciosa</i>Vahl
  作者：Luc Ruest、Marco Dodier、Hélène De Sève、Christian Lessard、Pascal Mongrain

  DOI：10.1139/v02-048

  日期：2002.5.1

  In a search for minor ryanoids from the plant Ryania Speciosa Vahl, we recently characterized 11 new members of that family of natural compounds. Most of them represent ryanodine (1) and dehydroryanodine (2) with a modified stage of oxidation in ring C. A second member of the new 4-deoxy series has been identified.Key words: minor natural ryanoids, ryanodine, dehydroryanodine, deoxyryanoids.

  为了从植物 Ryania Speciosa Vahl 中寻找次要的 ryanoids，我们最近鉴定了该天然化合物家族的 11 个新成员。它们中的大多数代表 ryanodine (1) 和 dehydroryanodine (2)，在环 C 中具有修饰的氧化阶段。新的 4-脱氧系列的第二个成员已被确定。关键词：次要天然 ryanoids，ryanodine，dehydroryanodine，deoxyryanoids。
• Bioactive ryanoids from nucleophilic additions to 4,12-seco-4,12-dioxoryanodine
  作者：Phillip R. Jefferies、Elisabeth Lehmberg、Wing Wah Lam、John E. Casida

  DOI：10.1021/jm00061a003

  日期：1993.4

  Ryanoids are the most potent inhibitors known for the calcium-release channel (ryanodine receptor), and they are also botanical insecticides. Twenty-two new ryanoids are described in which the C-4, C-12 bond is ruptured or replaced with an oxygen bridge and in which substituents at C-4 and C-12 are modified to have a wide range of polarities. They are obtained by nucleophilic additions to the 4,12-seco-4,12-dioxo compounds or diketones prepared from ryanodine and dehydroryanodine by periodate oxidation. Structures of the new compounds are distinguished by changes in NMR chemical shifts of C-13 and H-1 nuclei in the regions of C-4 and C-12. The new ryanoids are compared with ryanodine as inhibitors of [H-3] ryanodine binding using a rabbit muscle sarcoplasmic reticulum preparation alone or with ATP and a mouse brain receptor with ATP. They are also examined as knockdown agents for houseflies pretreated with a cytochrome P450 oxidase inhibitor to suppress detoxification and then injection with the ryanoid. The diketones have very weak binding activity in the receptor assays and very low toxicity to flies. Activity approaching that of ryanodine in both the receptor and fly assays is obtained for ketals with small groups at C-12 and polar substituents such as OH or NHOH at C-4. The oximes range from low to moderate potency. Addition of thiols to the vinyl group of dehydroryanodine gives three thioethers all of low biological activity. With most ryanoids addition of ATP to the muscle system increases its sensitivity to near that found for the brain receptor with ATP; possible exceptions are compounds with phenyl substituents. Activity at the calcium-release channel generally follows housefly toxicity although the hydrazine and hydroxyamine adducts are much weaker than expected perhaps due to dissociation under the assay conditions.
• Ryanodine Action at Calcium Release Channels. 1. Importance of Hydroxyl Substituents
  作者：Phillip R. Jefferies、Todd A. Blumenkopf、Peter J. Gengo、Loretta C. Cole、John E. Casida

  DOI：10.1021/jm950711l

  日期：1996.1.1

  Ryanodine (1) and dehydroryanodine (2) have a polar face formed by cis-hydroxyls at C-2, C-4, C-6, and C-12, The importance of the hydroxyls to the action of 1 and 2 at the ryanodine receptor (ryr) of calcium release channels is examined at [H-3]-1 binding sites in brain and skeletal muscle and in heart membranes relative to cardiac contractility, a pharmacologic response which appears to be mediated by the ryr. Five types of changes are considered: blocking the 4- and 6-hydroxyls as cyclic berates and boronates; blocking the 10- and 12-hydroxyls as cyclic phosphates, phosphonates, and phosphoramidates; methylation at nitrogen or hydroxyls at C-4 and C-10; dehydration of the C-2 hydroxyl; additional data for a 4,12-oxygen-bridged series. The first change has little effect on potency possibly due to the lability of the boron protective groups whereas the cyclic phosphorus compounds have reduced activity. Methylation reduces potency the least at nitrogen and the C-4 hydroxyl. Dehydration of 1 to 2-deoxy-2(13)-dehydro-1 allows the restoration of oxygen at C-2 by conversion to epoxides or a diol. One of the epoxides and 2-deoxy-2(13)-dehydro-2 retain 8-31% of ryanodine's potency in the ryr assails and 81% in the cardiac contractility system. In the 4,12-oxygen-bridged series, high potency at the receptor and cardiac muscle is retained in the 4-hydroxy ketal.
• Ryanodine Action at Calcium Release Channels. 2. Relation to Substituents of the Cyclohexane Ring
  作者：Phillip R. Jefferies、Peter J. Gengo、Michael J. Watson、John E. Casida

  DOI：10.1021/jm950712d

  日期：1996.1.1

  Ryanodine (1) and dehydroryanodine (2) are equipotent probes for the ryanodine receptor (ryr) of calcium release channels and differ only in 9(eq)-methyl for 1 and 9,21-methylene for 2. Ryanoids 1 and 2 are used here to prepare novel modifications of the cyclohexane substituents to determine their effects on ryr activity and selectivity. 10-0xo-1 when reacted with carbonyl and other reagents gave 13 C-10 derivatives including the epi-amine and epi-4-azidobenzoyl hydrazide as a candidate affinity probe. Four derivatives of 2 included the Delta(8)-10-hydroxy and Delta(8)-10-oxo compounds. Defunctionalization of the cyclohexane ring of 2 or its 4,6-ethylboronate was achieved :in part by controlled periodate oxidation of the 9,21-diol to the 21-nor-9-oxo compounds. These in turn provided access to the 9(ax)- and 9(eq)-hydroxy derivatives and to the 21-nor-10-deoxy-9-oxo compound which was converted to 21-nor-10-deoxy-1 and 10-deoxy-2 along with the epimeric 10-deoxy-9-hydroxy compounds. Ryanoids of similar potency to 1 as inhibitors of [H-3](-1) binding in mouse brain, rabbit skeletal muscle, and canine ventricle ryr preparations sind in a rat cardiac contractility assay (inhibition of mechanical response to electrical stimulation) are epi-l and the 10-epi-amino, 10-epi-methoxyamino, and 20-epi-azidobenzoyl hydrazide derivatives and 10-deoxydehydroryanodine. With a few exceptions the potency of the ryanoids at the cardiac ryr correlates well with their inhibition of cardiac contractility, indicating that the activity is associated with stabilizing the calcium release channel in a subconducting state, thereby uncoupling the excitation-contraction process.
• DESLONGCHAMPS, P.;BELANGER, A.;BERNEY, D. J. F.;BORSCHBERG, H. -J.;BROUSS+, CAN. J. CHEM., 68,(1990) N, C. 186-192
  作者：DESLONGCHAMPS, P.、BELANGER, A.、BERNEY, D. J. F.、BORSCHBERG, H. -J.、BROUSS+

  DOI：——

  日期：——