5,6-seco-5-oxo-3,4-cholesten-6-oic acid | 104527-35-7

• 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
• 英文名称: 5,6-seco-5-oxo-3,4-cholesten-6-oic acid
• 英文别名: 5,6-seco-5-oxocholest-3-en-6-oic acid；5-Oxo-5,6-secocholest-3-en-6-oic acid；5,6-seco-Cholest-3-en-5-on-6-saeure；[1-(1,5-Dimethyl-hexyl)-7a-methyl-5-(1-methyl-6-oxo-cyclohex-3-enyl)-octahydro-inden-4-yl]-acetic acid；2-[(1R,3aS,4S,5S,7aR)-7a-methyl-1-[(2R)-6-methylheptan-2-yl]-5-[(1R)-1-methyl-2-oxocyclohex-3-en-1-yl]-1,2,3,3a,4,5,6,7-octahydroinden-4-yl]acetic acid
• CAS: 104527-35-7
• 化学式: C₂₇H₄₄O₃
• 分子量: 416.645
• InChiKey: MVTQQYLVQMUYMS-VHHOZFFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5,6-seco-5-oxo-3,4-cholesten-6-oic acid 在 10percent Pd/C 氢气 作用下， 以 乙酸乙酯 为溶剂， 生成 5,6-seco-5-oxo-cholestan-6-oic acid
  参考文献：
  名称：

  Syntheses and Biological Activities of a Novel Group of Steroidal Derived Inhibitors for Human CDC25A Protein Phosphatase

  摘要：

  Silica gel supported pyrolysis of an azido-homo-oxa steroid led to rearrangement, presumably by a mechanism similar to that of solution phase Schmidt fragmentation, to produce a group of novel inhibitors for the oncogenic cell cycle regulator Cdc25A phosphatase. Cyano-containing acid 17, one of the best inhibitors in this group, inhibited the activity of Cdc25A protein phosphatase reversibly and noncompetitively with an IC50 value of 2.2 muM Structure-activity relationships revealed that a phosphate surrogate such as a carboxyl or a xanthate group is required for inhibitory activity, and a hydrophobic alkyl chain, such as the cholesteryl side chain, contributes greatly to the potency. Without the cyano group, acid 26 and xanthate 27 were found to be more selective over Cdc25A (IC50 = 5.1 muM and 1.1 muM, respectively) than toward CD45 (IC50 > 100 muM, in each case), a receptor protein tyrosine phosphatase. Several of these inhibitors showed antiproliferative activities in the NCI 60-human tumor cell line screen. These steroidal derived Cdc25 inhibitors provide unique leads for the development of dual-specificity protein phosphatase inhibitors.

  DOI：

  10.1021/jm0004401
• 作为产物：
  描述：

  胆固醇醋酸酯 在 吡啶 、 氯化亚砜 、 sodium azide 、 silica gel 、 臭氧 作用下， 以 二氯甲烷 、 丙酮 、 Petroleum ether 为溶剂， 反应 8.5h， 生成 5,6-seco-5-oxo-3,4-cholesten-6-oic acid
  参考文献：
  名称：

  Syntheses and Biological Activities of a Novel Group of Steroidal Derived Inhibitors for Human CDC25A Protein Phosphatase

  摘要：

  Silica gel supported pyrolysis of an azido-homo-oxa steroid led to rearrangement, presumably by a mechanism similar to that of solution phase Schmidt fragmentation, to produce a group of novel inhibitors for the oncogenic cell cycle regulator Cdc25A phosphatase. Cyano-containing acid 17, one of the best inhibitors in this group, inhibited the activity of Cdc25A protein phosphatase reversibly and noncompetitively with an IC50 value of 2.2 muM Structure-activity relationships revealed that a phosphate surrogate such as a carboxyl or a xanthate group is required for inhibitory activity, and a hydrophobic alkyl chain, such as the cholesteryl side chain, contributes greatly to the potency. Without the cyano group, acid 26 and xanthate 27 were found to be more selective over Cdc25A (IC50 = 5.1 muM and 1.1 muM, respectively) than toward CD45 (IC50 > 100 muM, in each case), a receptor protein tyrosine phosphatase. Several of these inhibitors showed antiproliferative activities in the NCI 60-human tumor cell line screen. These steroidal derived Cdc25 inhibitors provide unique leads for the development of dual-specificity protein phosphatase inhibitors.

  DOI：

  10.1021/jm0004401

文献信息

• Epoxidation and Baeyer–Villiger oxidation of γ-hydroxy-αβ-unsaturated ketones on exposure to m-chloroperbenzoic acid
  作者：Marioara Mendelovici、Erwin Glotter

  DOI：10.1039/p19920001735

  日期：——

  of 6β-and 6α-hydroxy-(acetoxy-)cholest-4-en-3-one with MCPBA gives two types of product, depending on the initial site of the peroxy acid attack. Attack at the carbonyl group gives a Baeyer–Villiger rearrangement leading first to enol lactones and then by epoxidation of the latter to epoxy lactones. Alternatively, attack at the double bond gives epoxy ketones which can subsequently undergo a Baeyer–Villiger

  用MCPBA处理3β-和3α-羟基（乙酰氧基）胆甾4烯-6和6β和6α-羟基（乙酰氧基）胆甾4烯-3产生两种类型的产物，取决于过氧酸侵蚀的初始部位。攻击羰基会产生Baeyer-Villiger重排，首先导致烯醇内酯，然后再将后者环氧化为环氧内酯。另外，对双键的进攻会产生环氧酮，随后会发生拜尔-维利格重排，从而生成环氧内酯。除了一个例外（3α-hydroxycholest-4-en-6-one），烯酮的Baeyer-Villiger氧化是主要过程。在轴向3α-或6β-乙酰氧基的存在下，双键的环氧化被抑制。
• Cdc25A Protein phosphatase inhibitors from anomalous ozonolysis of 5,6-seco-5-oxo-3-cholesten-6-oic acid
  作者：Hairuo Peng、Diane M Otterness、Robert T Abraham、Leon H Zalkow

  DOI：10.1016/s0040-4020(01)00043-6

  日期：2001.3

  Ozonolysis of the α,β-unsaturated keto acid, 5,6-seco-5-oxo-3-cholesten-6-oic acid (1), in ethyl acetate/acetic acid/water (15:15:1) at −20°C, followed by addition of piperidine, led to several novel lactone products (2–6), presumably formed through rearrangements of ozonide intermediates. The major product 2 was a lactone containing a dioxolane-4-one moiety, which exhibited a carbonyl stretching frequency

  在乙酸乙酯/乙酸/水（15：15：1）中，将α，β-不饱和酮酸5,6- seco -5-氧代-3-胆甾烯-6-酸（1）进行臭氧分解- 20℃，然后加入哌啶，导致了几个新的内酯产物（2 - 6），通过臭氧化物中间体的重排可能形成。主要产物2是含有二氧戊环-4-酮部分的内酯，其在1815cm -1处表现出羰基拉伸频率。。五种产物中的三种是由原料中的两个碳原子损失引起的，而不是α，β-不饱和酮的“异常臭氧分解”中通常观察到的一个碳原子的损失。这些化合物中的某些具有对人Cdc25A蛋白磷酸酶的适度抑制活性，该酶在几种人肿瘤细胞系中过表达。
• Norsteroids. III. Preparation of B-Norcholestane Derivatives by an Ester Condensation of a 5,6-seco-Cholestane Keto Ester¹
  作者：HAROLD R. NACE、ERNEST CAPSTACK

  DOI：10.1021/jo01070a058

  日期：1961.12
• Ahmad, M. S.; Moinuddin, G.; Ansari, Imtiaz A., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1984, vol. 23, # 3, p. 220 - 222
  作者：Ahmad, M. S.、Moinuddin, G.、Ansari, Imtiaz A.、Ansari, Shamim A.

  DOI：——

  日期：——
• Syntheses and Biological Activities of a Novel Group of Steroidal Derived Inhibitors for Human CDC25A Protein Phosphatase
  作者：Hairuo Peng、Wenge Xie、Diane M. Otterness、John P. Cogswell、Randy T. McConnell、H. Luke Carter、Garth Powis、Robert T. Abraham、Leon H. Zalkow

  DOI：10.1021/jm0004401

  日期：2001.3.1

  Silica gel supported pyrolysis of an azido-homo-oxa steroid led to rearrangement, presumably by a mechanism similar to that of solution phase Schmidt fragmentation, to produce a group of novel inhibitors for the oncogenic cell cycle regulator Cdc25A phosphatase. Cyano-containing acid 17, one of the best inhibitors in this group, inhibited the activity of Cdc25A protein phosphatase reversibly and noncompetitively with an IC50 value of 2.2 muM Structure-activity relationships revealed that a phosphate surrogate such as a carboxyl or a xanthate group is required for inhibitory activity, and a hydrophobic alkyl chain, such as the cholesteryl side chain, contributes greatly to the potency. Without the cyano group, acid 26 and xanthate 27 were found to be more selective over Cdc25A (IC50 = 5.1 muM and 1.1 muM, respectively) than toward CD45 (IC50 > 100 muM, in each case), a receptor protein tyrosine phosphatase. Several of these inhibitors showed antiproliferative activities in the NCI 60-human tumor cell line screen. These steroidal derived Cdc25 inhibitors provide unique leads for the development of dual-specificity protein phosphatase inhibitors.