methyl 11β,17α,20β-trihydroxy-3-oxo-1,4-pregnadiene-21-oate | 97274-84-5

• 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
• 英文名称: methyl 11β,17α,20β-trihydroxy-3-oxo-1,4-pregnadiene-21-oate
• 英文别名: methyl 11β,17α,20-trihydroxy-3-oxo-1,4-pregnadien-21-oate；methyl (20R)-11β,17,20-trihydroxy-3-oxo-1,4-pregnadien-21-oate；methyl (20S)-11β,17,20-trihydroxy-3-oxo-1,4-pregnadien-21-oate；methyl 20α-dihydroprednisolonate；Methyl 20alpha-dihydroprednisolonate；methyl (2S)-2-[(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-10,13-dimethyl-3-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-yl]-2-hydroxyacetate
• CAS: 97274-84-5
• 化学式: C₂₂H₃₀O₆
• 分子量: 390.477
• InChiKey: KGGJWTUYUOSWNH-ZWTXCLGESA-N

物化性质

• 沸点：
  580.4±50.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 11β,17α,20β-trihydroxy-3-oxo-1,4-pregnadiene-21-oate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以63%的产率得到(20S)-11β,17,20-trihydroxy-3-oxo-1,4-pregnadien-21-oic acid
  参考文献：
  名称：

  新的抗炎类固醇20-羧酰胺的合成：（20R）-和（20S）-21-（N-取代的氨基）-11β，17,20-三羟基-3,21-二氧代-1,4-孕二烯。

  摘要：

  新型甾体20-羧酰胺，（20R）-和（20S）-21-（N-取代的氨基）-11β，17,20-三羟基-3,21-二氧代-1,4-孕烷二烯的合成及抗炎活性描述。这些化合物是由20-二氢泼尼松酸的相应异构体（20R）-和（20S）-11β，17,20-三羟基-3-氧代-1,4-孕烯基-21-oic酸与N，N1-二环己基碳二亚胺（DCC）和1-羟基苯并三唑活化甾体酸后的伯胺 通过还原甲基（20R）-和（20S）-11 beta，17,20-三羟基-3-氧代-1,4-孕烷-21-甲基来实现20-甲酰胺在C-20的构型分配的确认。 （20R）-和（20S）-11 beta，17,20,21-tetrahydroxy-3-oxo-1在C-20的已知立体化学 4-孕烯二酮通过巴豆油诱导的耳部水肿试验评估了这些甾体20-羧酰胺的局部抗炎活性，并通过棉球颗粒肉芽肿生物试验评估了它们的局部和全身抗炎活性。这些

  DOI：

  10.1021/jm00395a011
• 作为产物：
  描述：

  methyl 20β-acetoxy-11β,17-dihydroxy-3-oxo-1,4-pregnadien-21-oate 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以89.2%的产率得到methyl 11β,17α,20β-trihydroxy-3-oxo-1,4-pregnadiene-21-oate
  参考文献：
  名称：

  General and facile method for determination of configuration of steroid-17-yl methyl glycolates at C-20 based on kinetic examination

  摘要：

  相应的类固醇、泼尼松龙、地塞米松和氢化可的松在绝对甲醇中与醋酸铜反应生成的异构体类固醇-17-基甲基羟酸酯的量曲线图，以及对其产物进行甲氧基羰基化的动力学检查，为确定类固醇-17-基甲基羟酸酯在 C-20 处的构型提供了一种通用而简便的方法。

  DOI：

  10.1039/a805276j

文献信息

• General method for determination of configuration of steroid-17-yl methyl glycolates at C-20.
  作者：Toshio SUZUKI、Hitoshi TADA、Yasuyuki MATSUDA、Xiao-hong YANG、Katsuo UNNO

  DOI：10.1248/cpb.41.1481

  日期：——

  Kinetic examination for methoxycarbonylations of the isomeric steroid-17-yl methyl glycolates at C-20 and plots of the amount of each isomer produced by a reaction of their corresponding steroids with cupric acetate in absolute methanol provide a general and facile method for determination of the configuration of the steroid-17-yl methyl glycolates at C-20.

  对 C-20 位的甾体-17-基甲基羟基化合物异构体的甲氧基羰基化进行动力学检查，并绘制出相应的甾体与醋酸铜在绝对甲醇中反应生成的每种异构体的量，为确定 C-20 位的甾体-17-基甲基羟基化合物的构型提供了一种通用而简便的方法。
• Examination of Local Anti-inflammatory Activities of New Steroids, Hemisuccinyl Methyl Glycolates.
  作者：Toshio SUZUKI、Etsuko SATO、Hitoshi TADA、Yoichi TOJIMA

  DOI：10.1248/bpb.22.816

  日期：——

  To overcome the side effects of steroids, novel steroid-17-yl methyl glycolates with succinyl group at C-20, derived from predinisolone and dexamethasone were prepared based on concept of the antedrug. Their topical anti-inflammatory activity and systemic effects were evaluated trough croton oil-induced ear edema and paper disk granuloma bioassay. Among them, (20S)-succinyl dexamethasone derivatives (7 and 11) indicated more potent ati-inflammatory activity than the parent dexamethasone and did not show corticosteroidal side effects of thymic, adrenal involution or body weight loss. Both 7 and 11 were immediately metabolized into active compound 3 and this metabolite was eliminated with mean half-lives of 0.786 to 0.866 h in rat serum. Our findings suggest that these two compounds might be candidates as the novel steroids, and that that introduction of the succinyl group into the methyl glycolates at C-20 is useful to avoid suppressiion of organs due to the side effects of corticosteroids.

  为了克服类固醇的副作用，研究人员根据抗药物的概念，从predinisolone和地塞米松中提取出了C-20位琥珀酰基的新型类固醇-17-基甲基羟基化合物。通过巴豆油诱导的耳水肿和纸盘肉芽肿生物测定评估了它们的局部抗炎活性和全身作用。其中，(20S)-琥珀酰地塞米松衍生物（7 和 11）比母体地塞米松具有更强的抗炎活性，而且不会出现胸腺、肾上腺萎缩或体重减轻等皮质类固醇副作用。7 和 11 会立即代谢为活性化合物 3，这种代谢物在大鼠血清中的平均半衰期为 0.786 至 0.866 小时。我们的研究结果表明，这两种化合物可能是新型类固醇的候选化合物，在甲基羟基化合物的 C-20 处引入琥珀酰基有助于避免皮质类固醇的副作用对器官的抑制。
• Cu‐Catalyzed Tandem Oxidation‐Intramolecular Cannizzaro Reaction of Biorenewables and Bioactive Molecules
  作者：Hristo Petkov、Martin A. Ravutsov、Manuel J. Verganista、Yavor N. Mitrev、Nuno R. Candeias、Svilen P. Simeonov

  DOI：10.1002/cssc.202400013

  日期：——

  A Cu-catalyzed tandem oxidation-intramolecular Cannizzaro reaction that converts α-hydroxyketones into valuable α-hydroxyesters under mild conditions is reported. The substrate scope encompasses biorenewable synthons and complex structures, such as steroids. We provided mechanistic insights using isotope labeling and rationalization by computational means.

  据报道，铜催化的串联氧化-分子内坎尼扎罗反应可在温和条件下将 α-羟基酮转化为有价值的 α-羟基酯。底物范围包括生物可再生合成子和复杂结构，例如类固醇。我们使用同位素标记和计算手段合理化提供了机制见解。
• Synthesis, isolation, and characterization of the cis and trans isomers of steroidal 20-hydroxy-17(20)-en-21-aldehydes
  作者：Marvin L. Lewbart、Carl Monder、Walter J. Boyko、Carol J. Singer、F. Iohan

  DOI：10.1021/jo00267a019

  日期：1989.3
• Effect of chirality at C-20 of methyl 11β,17α,20-trihydroxy-3-oxo-1,4-pregnadien-21-oate derivatives on antiinflammatory activity
  作者：Zhengqing You、Ann S Heiman、Charles E Hudson、Henry Joung Lee

  DOI：10.1016/s0039-128x(01)00189-1

  日期：2002.4

  In an effort to determine the C-20 chirality effect on the antiinflammatory activity of 17beta-glycolate esters, methyl 11beta,17alpha,20-trihydroxy-3-oxo-1,4-pregnadien-21-oate and its 9alpha-fluoro analog, their acetonide and their carbonate derivatives were synthesized and evaluated. The agents were tested for their binding potency to the macrophage glucocorticoid receptor, and their effect on LPS-induced nitric oxide generation in RAW 264.7 cells. The acetonide derivatives showed the highest binding affinity while the triols and carbonates bound rather poorly to the receptors. With the exception of the triols, the a-isomer in each pair of the agents exhibited higher binding affinity to the receptor than its corresponding beta-isomer, clearly indicating that C-20 chirality has a significant effect on anti inflammatory activity. In addition, the alpha-isomers of the acetonides showed substantially higher binding affinity than the parent compound, prednisolone. In contrast to the high binding activity exhibited by some of the acetonides, all of the agents showed weak inhibitory effect on NO generation. Metabolic inactivation during assessment of NO inhibition may play it role in the divergence noted between receptor affinity and the measured biologic activity resulting from the binding. (C) 2002 Elsevier Science Inc. All rights reserved.