4-[(3S,5R,8R,9S,10S,12R,13S,14S,17R)-3-[(2R,4S,5S,6R)-4,5-二羟基-6-甲基四氢吡喃-2-基]氧基-12,14-二羟基-10,13-二甲基-1,2,3,4,5,6,7,8,9,11,12,15,16,17-十四氢环戊烯并[a]菲-17-基]-5H-呋喃-2-酮 | 5352-63-6

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 中文名称: 4-[(3S,5R,8R,9S,10S,12R,13S,14S,17R)-3-[(2R,4S,5S,6R)-4,5-二羟基-6-甲基四氢吡喃-2-基]氧基-12,14-二羟基-10,13-二甲基-1,2,3,4,5,6,7,8,9,11,12,15,16,17-十四氢环戊烯并[a]菲-17-基]-5H-呋喃-2-酮
• 中文别名: 异羟基洋地黄毒甙元单洋地黄毒糖甙；地高辛杂质D
• 英文名称: Digoxigenin mono-digitoside
• 英文别名: digoxigenin mono-digitoxoside；digoxigenin monodigitoxoside；monodigitoxosyldigoxigenin；Monodigitoxoside；3β-(β-D-ribo-2,6-dideoxy-hexopyranosyloxy)-12β,14-dihydroxy-5β,14β-card-20(22)-enolide；3β-(β-D-ribo-2,6-Didesoxy-hexopyranosyloxy)-12β,14-dihydroxy-5β,14β-card-20(22)-enolid；3-[(3S,5R,8R,9S,10S,12R,13S,14S,17R)-3-[(2R,4S,5S,6R)-4,5-dihydroxy-6-methyloxan-2-yl]oxy-12,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one
• CAS: 5352-63-6
• 化学式: C₂₉H₄₄O₈
• 分子量: 520.664
• InChiKey: JFSXBMIFXZFKHD-ZDDLGXCGSA-N

物化性质

• 熔点：
  228-230°C
• 沸点：
  708.3±60.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO：微溶；甲醇：微溶

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  37
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  8

安全信息

• 储存条件：
  -20°C，密闭保存，干燥环境

制备方法与用途

地高辛是一种钠/钾+ATP酶抑制剂，同时也是强心苷的代谢产物。

反应信息

• 作为反应物：
  描述：

  4-[(3S,5R,8R,9S,10S,12R,13S,14S,17R)-3-[(2R,4S,5S,6R)-4,5-二羟基-6-甲基四氢吡喃-2-基]氧基-12,14-二羟基-10,13-二甲基-1,2,3,4,5,6,7,8,9,11,12,15,16,17-十四氢环戊烯并[a]菲-17-基]-5H-呋喃-2-酮 以 甲醇 为溶剂， 反应 0.25h， 生成 地黄苷元
  参考文献：
  名称：

  Metabolism of digoxin and digoxigenin digitoxosides in rat liver microsomes: involvement of cytochrome P4503A

  摘要：

  1. The sequential metabolism of digoxin (Dg3) to digoxigenin bis-digitoxoside (Dg2), digoxigenin mono-digitoxoside (Dg1) and digoxigenin (Dg0) was investigated in rat liver microsomes.2. Kinetic studies produced results consistent with a single enzyme mechanism describing the successive oxidative cleavages. Formation of Dg2 was catalysed with mean (+/- SD) K-m and V-max of 125 +/- 22 mu M and 362 +/- 37 pmol/min/mg protein, respectively. The corresponding values for the formation of Dg1 were 61 +/- 5 mu M and 7 +/- 1 pmol/min/mg protein. Dg0 formation was catalysed with the apparent values of 30 +/-9 mu M and 310 +/- 30 pmol/min/mg protein.3. Chemical inhibition of cytochrome P450 (CYP) 3A subfamily with ketoconazole and triacetyoleandomycin decreased the formation of Dg2 and Dg1 by up to 90%. Antibodies specific to rat CYP3A2 lowered the rate of oxidative cleavage of Dg3 and Dg2 by up to 85%. Inhibition of CYP2E1, CYP2C subfamily and CYP1A2 by chemical and immunoinhibition did not affect initial rates of metabolism of Dg3 and Dg2. In contrast, Dg1 metabolism was not affected by triacetyloleandomycin as well as by antibodies to CYP3A2, CYP2C11, CYP2E1, CYP2B1/2B2 and CYP1A2. It was however inhibited by 1 80% by gestodene and 17 alpha-ethynylestradiol (selective inhibitors of human CYP3A).4. Collectively, these data support the involvement of CYP3A in the cleavage of Dg3 and Dg2 in rat liver microsomes. The enzyme-metabolizing Dg1 remains to be identified.

  DOI：

  10.1080/004982599238722
• 作为产物：
  描述：

  地高辛 在 aqueous acid 作用下， 生成 4-[(3S,5R,8R,9S,10S,12R,13S,14S,17R)-3-[(2R,4S,5S,6R)-4,5-二羟基-6-甲基四氢吡喃-2-基]氧基-12,14-二羟基-10,13-二甲基-1,2,3,4,5,6,7,8,9,11,12,15,16,17-十四氢环戊烯并[a]菲-17-基]-5H-呋喃-2-酮
  参考文献：
  名称：

  Digoxigenin-mono- und -bis-digitoxosid, zwei neue Glykoside der Digitalis lanata

  摘要：

  DOI：

  10.1007/bf01177965

文献信息

• Effects of cyclodextrins on the acid hydrolysis of digoxin
  作者：K UEKAMA、T FUJINAGA、F HIRAYAMA、M OTAGIRI、Y KURONO、K IKEDA

  DOI：10.1111/j.2042-7158.1982.tb04690.x

  日期：2011.4.12

  The effects of three cyclodextrins (α-, β-, γ-CyD) on the acid hydrolysis of digoxin were examined. From the high performance liquid chromatographic tracing of each of the four components (digoxin, bisdigitoxoside, monodigitoxoside, digoxigenin) in reaction mixtures, the individual rate constants (k1-k6) were determined by analogue computer simulation. The hydrolysis was suppressed by CyDs in the order of β->γ->α-CyD, where β-CyD inhibited the appearance rates of digoxigenin (k3, k5, and k6) significantly. In the dissolution study of digoxin tablets, the increase in dissolution rate and decrease in acid hydrolysis were attained by inclusion complexation. The data are presented suggesting that CyDs are useful for improving the oral bioavailability of digoxin.

  标题：摘要 研究了三种环糊精（α-，β-，γ-CyD）对洋地黄酸水解的影响。通过对反应混合物中四种成分（洋地黄，双洋地黄苷，单洋地黄苷，洋地黄素）的每个成分的高效液相色谱追踪，通过模拟计算机模拟确定了各自的速率常数（k1-k6）。水解被CyDs抑制的顺序为β->γ->α-CyD，其中β-CyD显著抑制了洋地黄素的出现速率（k3，k5和k6）。在洋地黄片剂的溶解研究中，通过包合络合增加了溶解速率并减少了酸水解。数据显示，CyDs对于提高洋地黄的口服生物利用度是有用的。
• Regioselective schiff's base mediated deglycosidation of digitalis glycosides. New efficient synthesis of digoxigenin bis-digitoxoside and digoxigenin mono-digitoxoside
  作者：Maciej Adamczyk、Jonathan Grote

  DOI：10.1016/0040-4039(94)02212-t

  日期：1995.1

  Dialdehydes derived from digoxin glycosides via sodium periodate oxidation were regioselectively deglycosylated by various amino acids in anhydrous methanolic solution to afford excellent yields of digoxigenin bis-digitoxoside and digoxigenin mono-digitoxoside in a single step.
• [EN] BIOMARKERS OF REDUCED INSULIN ACTION<br/>[FR] MARQUEURS BIOLOGIQUES D'UNE ACTION RÉDUITE DE L'INSULINE
  申请人：MAYO FOUNDATION

  公开号：WO2012058298A1

  公开（公告）日：2012-05-03

  This document provides methods and materials for assessing metabolic disorders related to reduced insulin action (e.g. insulin resistance or insulin deficiency) in a mammal (e.g. human). For example, methods and materials for assessing insulin resistance, risk of developing insulin resistance and monitoring efficacy of insulin resistance treatment are provided.