3-羟基-5-胆甾烯酸 | 6561-58-6

• 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: 3-羟基-5-胆甾烯酸
• 英文名称: 3β-hydroxy-5-cholestenoic acid
• 英文别名: 3β-hydroxycholest-5-en-26-oic acid；3-β-hydroxy-5-cholesten-27-oic acid；5-cholestenoic acid；(25Ξ)-3β-hydroxy-cholest-5-en-26-oic acid；(25Ξ)-3β-Hydroxy-cholest-5-en-26-saeure；cholesterol-27 acid；3-Hydroxy-5-cholestenoic acid；(6R)-6-[(3S,8S,9S,10R,13R,14S,17R)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-methylheptanoic acid
• CAS: 6561-58-6
• 化学式: C₂₇H₄₄O₃
• 分子量: 416.645
• InChiKey: WVXOMPRLWLXFAP-AMQKJUDNSA-N

物化性质

• 熔点：
  178-180°C
• 溶解度：
  可溶于DMSO

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-羟基-5-胆甾烯酸 在 吡啶 、 copper(ll) bromide 作用下， 以 溶剂黄146 为溶剂， 反应 0.08h， 生成 (R)-6-((3S,7S,8S,9S,10R,13R,14S,17R)-3-Acetoxy-7-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-methyl-heptanoic acid methyl ester
  参考文献：
  名称：

  Synthesis of potential C27-intermediates in bile acid biosynthesis and their deuterium-labeled analogs

  摘要：

  In connection with studies of alternative pathways in bile acid biosynthesis, potential intermediates in a pathway starting with 27-hydroxylation of cholesterol have been prepared in natural and deuterated forms. Established methods were used to prepare 27-hydroxycholesterol and 3beta-hydroxy-5-cholestenoic acid. Clemmensen reduction of kryptogenin in unlabeled and deuterated solvents yielded 27-hydroxy-cholesterol and 16-oxo-5-cholestene-3beta,27-diol, which were separated by adsorption chromatography on Unisil. The labeled 27-hydroxycholesterol and 3beta-hydroxy-5-cholestenoic acid derived from it consisted of molecules with seven (50%), six (20%), and eight (20%) deuterium atoms, and unlabeled molecules were not detected. The acetates of 27-hydroxycholesterol and methyl 3beta-hydroxy-5-cholestenoate were 7alpha-hydroxylated in a copper-catalyzed reaction with tert-butylperbenzoate, and the products were purified by chromatography on Unisil. The 7beta-epimers were obtained as side products. Labeled 3beta,7alpha-dihydroxy-5-cholenoic acid was prepared in the same way from 3beta-hydroxy-5-[2,2,4,4,23-H-2(5)-cholenoic acid. The 3-oxo-DELTA4 analogs of the 3beta-hydroxy-DELTA5 compounds were prepared by oxidation with cholesterol oxidase. The labeled products had the same isotopic composition as the starting materials. Gas chromatographic retention indices and mass spectral characteristics of the trimethylsilyl ether derivatives of the neutral steroid and the methylated acids are given for all compounds.

  DOI：

  10.1016/0039-128x(93)90048-r
• 作为产物：
  描述：

  3-O-乙酰基-26-羟基胆固醇 在 甲醇 、 氢氧化钾 、 jones reagent 作用下， 以 丙酮 为溶剂， 反应 0.25h， 生成 3-羟基-5-胆甾烯酸
  参考文献：
  名称：

  Synthesis of potential C27-intermediates in bile acid biosynthesis and their deuterium-labeled analogs

  摘要：

  In connection with studies of alternative pathways in bile acid biosynthesis, potential intermediates in a pathway starting with 27-hydroxylation of cholesterol have been prepared in natural and deuterated forms. Established methods were used to prepare 27-hydroxycholesterol and 3beta-hydroxy-5-cholestenoic acid. Clemmensen reduction of kryptogenin in unlabeled and deuterated solvents yielded 27-hydroxy-cholesterol and 16-oxo-5-cholestene-3beta,27-diol, which were separated by adsorption chromatography on Unisil. The labeled 27-hydroxycholesterol and 3beta-hydroxy-5-cholestenoic acid derived from it consisted of molecules with seven (50%), six (20%), and eight (20%) deuterium atoms, and unlabeled molecules were not detected. The acetates of 27-hydroxycholesterol and methyl 3beta-hydroxy-5-cholestenoate were 7alpha-hydroxylated in a copper-catalyzed reaction with tert-butylperbenzoate, and the products were purified by chromatography on Unisil. The 7beta-epimers were obtained as side products. Labeled 3beta,7alpha-dihydroxy-5-cholenoic acid was prepared in the same way from 3beta-hydroxy-5-[2,2,4,4,23-H-2(5)-cholenoic acid. The 3-oxo-DELTA4 analogs of the 3beta-hydroxy-DELTA5 compounds were prepared by oxidation with cholesterol oxidase. The labeled products had the same isotopic composition as the starting materials. Gas chromatographic retention indices and mass spectral characteristics of the trimethylsilyl ether derivatives of the neutral steroid and the methylated acids are given for all compounds.

  DOI：

  10.1016/0039-128x(93)90048-r

文献信息

• Structural and Biochemical Characterization of Mycobacterium tuberculosis CYP142
  作者：Max D. Driscoll、Kirsty J. McLean、Colin Levy、Natalia Mast、Irina A. Pikuleva、Pierre Lafite、Stephen E.J. Rigby、David Leys、Andrew W. Munro

  DOI：10.1074/jbc.m110.164293

  日期：2010.12

  M. tuberculosis CYP125, but having a near-identical organization of distal pocket residues to the branched fatty acid oxidizing M. tuberculosis CYP124. The cholesterol oxidizing activity of CYP142 provides an explanation for previous findings that DeltaCYP125 strains of Mycobacterium bovis and M. bovis BCG cannot grow on cholesterol, because these strains have a defective CYP142 gene. CYP142 is revealed

  结核分枝杆菌细胞色素 P450 酶 CYP142 由参与宿主胆固醇代谢的大型基因簇编码。 CYP142 被表达并纯化为可溶性低自旋 P450 血红素蛋白。 CYP142 与胆固醇及其氧化衍生物 cholest-4-en-3-one 紧密结合，使血红素铁广泛转变为高自旋状态。证明了对唑类抗生素的高亲和力，突出了它们的治疗潜力。 CYP142 催化胆固醇/cholest-4-en-3-one 的 27-羟基化，或通过连续的甾醇氧化从这些底物生成 5-胆烯酸/cholestenic-en-3-one-27-oic 酸，催化结果取决于所使用的氧化还原伙伴系统。 CYP142晶体结构解析为1.6 A，揭示了与胆固醇代谢结核分枝杆菌CYP125相似的活性位点组织，但具有与支链脂肪酸氧化结核分枝杆菌CYP124几乎相同的远端口袋残基组织。 CYP142 的胆固醇氧化活性为之前的发现提供了解释，即牛分枝杆菌和牛分枝杆菌
• Novel class of sterol ligands and their uses in regulation of cholesterol and gene expression
  申请人：Javitt B. Norman

  公开号：US20060121024A1

  公开（公告）日：2006-06-08

  This invention relates to oxysteroids and oxysteroid hormones which have been identified. These oxysteroids are C27 modified sterols, particularly derivatives of intermediates in cholesterol synthesis, including lanosterol, zymosterol and desmosterol, including C27 diol and C27 acid derivatives, as well as related compounds and analogs thereof. The oxysteroids are capable of binding to or otherwise interacting with orphan nuclear receptors to result in modulation of gene expression. The invention further relates to methods of modulating the rate of cholesterol synthesis in a mammal. More specifically, the invention relates to treatment of cholesterol-related conditions which are improved or ameliorated by modulating the rate of cholesterol synthesis or cholesterol metabolism in a human in need thereof by administration of these oxysteroids, analogs or antagonists thereof. The invention includes methods for ameliorating, treating or preventing macular degeneration in a mammal comprising administering to said mammal an agent which stimulates or enhances the expression or activity of steroid sulphotransferase (SLUT2), particularly SLUT2B1b, or which stimulates or enhances the expression or activity of CYP27A1 or sterol 27-hydroxylase or otherwise increasing the sulfonation or 27-hydroxylation of cholesterol intermediates, including 7-ketocholesterol. Assays for identification of analogs, antagonists or modulators of these oxysteroids or of sterol 27-hydroxylase are also provided.

  本发明涉及已经鉴定的氧化甾体和氧化甾体激素。这些氧化甾体是C27修饰类固醇，特别是胆固醇合成中间体的衍生物，包括鲸蜡醇、酵母蜡醇和脱酸酶醇，包括C27二醇和C27酸衍生物，以及相关化合物和类似物。这些氧化甾体能够与孤儿核受体结合或以其他方式相互作用，从而调节基因表达。本发明进一步涉及在哺乳动物中调节胆固醇合成速率的方法。更具体地，本发明涉及通过给予这些氧化甾体、类似物或其拮抗剂来改善或缓解需要调节胆固醇合成或胆固醇代谢速率的人类的与胆固醇相关的疾病的治疗。本发明包括治疗、改善或预防哺乳动物黄斑退化的方法，包括给予一种刺激或增强类固醇硫酸转移酶（SLUT2），特别是SLUT2B1b，表达或活性的药物，或者刺激或增强CYP27A1或类固醇27-羟化酶的表达或活性，或以其他方式增加胆固醇中间体的磺酸化或27-羟化，包括7-酮胆固醇。还提供了用于鉴定这些氧化甾体或类固醇27-羟化酶的类似物、拮抗剂或调节剂的测定方法。
• Compound and method for the treatment and diagnosis of neurodegenerative conditions
  申请人：SWANSEA UNIVERSITY

  公开号：US10226475B2

  公开（公告）日：2019-03-12

  A reagent selected from cholestenoic acid or an inhibitor of an enzyme in the cholestenoic acid biosynthetic or metabolic pathway for use in the treatment of neurodegenerative conditions. In particular, the reagent is a cholestenoic acid of a particular form, such as 3β,7α-dihydroxycholest-5-en-26-oic (3β,7α-diHCA), not previously associated with neural tissue or CSF. Pharmaceutical compositions, methods of treatment or prevention of neurodegenerative conditions as well as diagnostic methods and novel biomarkers form further aspects of the invention.

  一种选自胆烯酸或胆烯酸生物合成或代谢途径中酶的抑制剂的试剂，用于治疗神经退行性疾病。特别是，该试剂是一种特殊形式的胆甾烯酸，如 3β,7α-二羟基胆甾烯-5-烯-26-酸（3β,7α-diHCA），以前与神经组织或 CSF 无关。本发明还包括药物组合物、治疗或预防神经退行性疾病的方法以及诊断方法和新型生物标记物。
• Methods for diagnosing motor neuron diseases
  申请人：SWANSEA UNIVERSITY

  公开号：US11536730B2

  公开（公告）日：2022-12-27

  The invention relates to methods for determining whether a subject is afflicted with a motor neuron disease, the method comprising conducting an analysis of cerebrospinal fluid and/or plasma, measuring the level of one or more sterol/oxysterol analytes, and comparing these to reference values. Further, the invention relates to methods of identifying agents suitable for the treatment of MND, and monitoring the progress of the disease.

  本发明涉及确定受试者是否患有运动神经元疾病的方法，该方法包括对脑脊液和/或血浆进行分析，测量一种或多种甾醇/氧甾醇分析物的水平，并将其与参考值进行比较。 此外，本发明还涉及鉴定适用于治疗运动神经元疾病的药物和监测疾病进展的方法。
• Kucera; Sorm, Collection of Czechoslovak Chemical Communications, 1958, vol. 23, p. 116,123
  作者：Kucera、Sorm

  DOI：——

  日期：——