9,21-二氢-鱼尼丁-3-(1H-吡咯-2-羧酸) | 94513-55-0

• 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: 9,21-二氢-鱼尼丁-3-(1H-吡咯-2-羧酸)
• 中文别名: 9,21-二脱氧兰尼碱
• 英文名称: 9,21-dehydroryanodine
• 英文别名: Dehydroryanodine；[(1R,2R,6S,7S,9S,10S,11S,12R,13S,14R)-2,6,9,11,13,14-hexahydroxy-7,10-dimethyl-3-methylidene-11-propan-2-yl-15-oxapentacyclo[7.5.1.01,6.07,13.010,14]pentadecan-12-yl] 1H-pyrrole-2-carboxylate
• CAS: 94513-55-0
• 化学式: C₂₅H₃₃NO₉
• 分子量: 491.538
• InChiKey: BPFNBBLVUYSFRK-OHEPIYSBSA-N

物化性质

• 沸点：
  724.3±60.0 °C(Predicted)
• 密度：
  1.57±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  173
• 氢给体数：
  7
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  9,21-二氢-鱼尼丁-3-(1H-吡咯-2-羧酸) 在 palladium on activated charcoal 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 5.17h， 生成 [(1R,6S,7S,9S,10S,11S,12R,13S,14R)-6,9,11,13,14-pentahydroxy-3,7,10-trimethyl-2-oxo-11-propan-2-yl-15-oxapentacyclo[7.5.1.01,6.07,13.010,14]pentadec-3-en-12-yl] 1H-pyrrole-2-carboxylate
  参考文献：
  名称：

  Ryanodine Action at Calcium Release Channels. 2. Relation to Substituents of the Cyclohexane Ring

  摘要：

  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.

  DOI：

  10.1021/jm950712d

文献信息

• Structural aspects of ryanodine action and selectivity
  作者：Andrew L. Waterhouse、Issac N. Pessah、Alexander O. Francini、John E. Casida

  DOI：10.1021/jm00387a022

  日期：1987.4

  The topography and toxicological relevance of the Ca2+-ryanodine receptor complex are evaluated with ryanodine and two natural analogues (9,21-didehydro and the new 18-hydroxy), 13 ryanoid derivatives (prepared from ryanodine and didehydroryanodine by functionalizing the available pyrrole, olefin, and hydroxyl substituents), and four degradation products. The potency of ryanoids at the skeletal muscle

  Ca2 + -ryanodine受体复合物的拓扑结构和毒理学相关性通过使用ryanodine和两种天然类似物（9,21-didehydro和新的18-羟基）和13种ryanoid衍生物（由ryanodine和didehydrohydroanoanodine制备）来评估，方法是将可用的吡咯，烯烃官能化和羟基取代基），以及四种降解产物。在骨骼肌肌质网特异性结合位点上的类红素的效力通常与它们对小鼠的毒性平行，从而支持了Ca2 +-ryanodine受体的毒理学意义。通过在异丙基甲基取代基上的羟基化，在C9上的差向异构化，在C10-羟基上的氧化或乙酰化，或在9,21位上的环氧化，可以使ryanodine和didehydroryanodine的最佳受体效能降低3-14倍。其他类瑞安糖活性较低。
• Derivatives of ryanodine and dehydroryanodine
  申请人：Indiana University Foundation

  公开号：US05432288A1

  公开（公告）日：1995-07-11

  Novel O.sub.10eq -derivatives of ryanodine and dehydroryanodine characterized as binding strongly to ryanodine receptor, useful in affecting Ca.sup.++ efflux in tissue and also in isolating ryanodine receptor from sarcoplasmic reticulum. Also described are novel radio-iodinated alanine derivatives useful to radio label ryanodine and dehydroryanodine derivatives.

  小说O.sub.10eq-瑞芬酮和脱水瑞芬酮的衍生物具有强烈结合瑞芬酮受体的特性，对影响组织中的Ca.sup.++外流以及从肌浆网中分离瑞芬酮受体非常有用。还描述了新型放射性碘化丙氨酸衍生物，可用于放射性标记瑞芬酮和脱水瑞芬酮的衍生物。
• 9, 21-Didehydroryanodine: a new principal toxic constituent of the botanical insecticide Ryania
  作者：Andrew L. Waterhouse、Ian Holden、John E. Casida

  DOI：10.1039/c39840001265

  日期：——

  A major insecticidal constituent of Ryania speciosa is isolated and characterized by n.m.r. and mass spectroscopy as the new alkaloid 9, 21-didehydroryanodine (2); reduction of (2) with hydrogen (or tritium)gas yields both ryanodine (1) and 9-epiryanodine (3)(or their 9,21-3H analogues) in a 1:9 ratio.

  分离出了Ryania speciosa的主要杀虫成分，并通过核磁共振和质谱法鉴定为新的生物碱9、21-二氢加氢精氨酸（2）。还原的（2用氢气（或氚）气体），得到两个兰诺定（1）和9- epiryanodine（3）（或它们的9,21- 3 ħ类似物）以1：9的比例。
• 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.
• Characterisation of antibody models of the ryanodine receptor for use in high-throughput screening†
  作者：Andrew J. Dinsmore、William Rees-Blanchard、Philip Bentley、Terence Lewis、Steven D. Kahl、Peter S. McPherson、Michael J. Mullinnix、Kevin P. Campbell、John D. Windass、Fergus G. P. Earley

  DOI：10.1002/(sici)1096-9063(199812)54:4<345::aid-ps825>3.0.co;2-h

  日期：1998.12

  The syntheses of seven novel synthetic analogues of the naturally occurring insecticide ryanodine are described. These, and other synthetic and naturally occurring analogues, have been used to characterise the selectivity of a monoclonal antibody which has been produced by immunisation with 9-hydroxy-21-(4-azidobenzyloxy)-9-epiryanodine photo-conjugated to keyhole limpet haemocyanin. The antibody binds [H-3]ryanodine with a dissociation constant of 0.37 nM. The specificity of this antibody in terms of its ability to recognise 11 natural and synthetic analogues of ryanodine has been determined by [H-3]ryanodine displacement and shown to be similar (for a partially overlapping set of analogues) to that determined earlier for a rabbit polyclonal antibody (Kahl, S. D., er al., Anal. Biochem., 218 (1994) 55-62). The selectivity of the antibodies is shown to be related to that of the sarcoplasmic reticulum Ca2+ release channel from rabbit skeletal muscle, both for this set of ryanodine analogues and for three structurally dissimilar, low-molecular-weight compounds identified by high-throughput screening. The advantages of these antibody models of the Ca2+ release channel for screening are illustrated by their superior performance in a homogeneous binding assay. (C) 1998 Society of Chemical Industry.