cholest-5-ene-3β,7β-diol diacetate | 18099-24-6

• 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
• 英文名称: cholest-5-ene-3β,7β-diol diacetate
• 英文别名: 3β,7β-diacetoxycholest-5-ene；[(3S,7R,8S,9S,10R,13R,14S,17R)-7-acetyloxy-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl] acetate
• CAS: 18099-24-6
• 化学式: C₃₁H₅₀O₄
• 分子量: 486.736
• InChiKey: QAEWQLKVBODSFK-HXPLWBQQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.6
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  cholest-5-ene-3β,7β-diol diacetate 在 高氯酸 、 lipase AY 、 间氯过氧苯甲酸 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 、 丙酮 、 甲苯 为溶剂， 反应 74.0h， 生成 5α,6β,7β-trihydroxycholestan-3β-yl acetate
  参考文献：
  名称：

  Selective Cytotoxicity of Oxysterols through Structural Modulation on Rings A and B. Synthesis, in Vitro Evaluation, and SAR

  摘要：

  Chemically diverse oxysterols were prepared and evaluated for cytotoxicity, aiming to push forward potency and selectivity. They were tested against seven cancer (HT-29, HepG2, A549, PC3, LAMA-84, MCF-7, and SH-SYSY) and two noncancerous cell lines (ARPE-19 and BJ). The influence of the oxidation pattern on rings A and B was studied. Oxygen functionalities on ring B, such as oxo, oxime, acetamide, acetate, and alkoxy, were evaluated. Most oxysterols were cytotoxic in the low micromolar range, with emphasis to the tetrols 14 and 34, the 6 beta methoxy and acetoxy derivatives 21 and 45, and the oxime 28. In general, the oxysterols were more toxic to cancer cells and a set of compounds (9, 14, 21, 28, 45) with very high selectivity was identified. The cytotoxicity of 3 beta-acetates was lower than that of the parent alcohols, although incubation for a longer period rendered them equally cytotoxic, pointing them as potential prodrugs of oxysterols.

  DOI：

  10.1021/jm200803d
• 作为产物：
  描述：

  cholesterol 在 吡啶 作用下， 生成 cholest-5-ene-3β,7β-diol diacetate
  参考文献：
  名称：

  On the Epimeric 7-Hydroxycholesterols

  摘要：

  DOI：

  10.1021/ja01262a067

文献信息

• Sterol synthesis. Preparation and characterization of fluorinated and deuterated analogs of oxygenated derivatives of cholesterol
  作者：Shengrong Li、Jihai Pang、William K. Wilson、George J. Schroepfer, Jr.

  DOI：10.1016/s0009-3084(99)00005-5

  日期：1999.5

  preparation, purification and characterization of 43 oxygenated sterols, including the 4 beta-hydroxy, 7 alpha-hydroxy, 7 beta-hydroxy, 7-keto, and 19-hydroxy derivatives of cholesterol and their analogs with 25,26,26,26,27,27,27-heptafluoro (F7) and 26,26,26,27,27,27-hexadeuterio (d6) substitution. The 7 alpha-hydroxy, 7 beta-hydroxy, and 7-keto derivatives of (25R)-cholest-5-ene-3 beta, 26-diol (1d) and their

  氧化的固醇，包括自氧化产物和固醇代谢产物，都具有许多重要的生物学活性。可靠标准品的提供大大简化了通过色谱和光谱法鉴定和定量氧固醇的方法，氘代和氟化类似物作为定量内标非常有价值。我们描述了43种含氧固醇的制备，纯化和表征，包括胆固醇及其类似物与25,26,26的4β-羟基，7α-羟基，7β-羟基，7-酮和19-羟基衍生物，26,27,27,27-七氟（F7）和26,26,26,27,27,27-六氘（d6）取代。还制备了（25R）-胆甾-5-烯-3β，26-二醇（1d）的7α-羟基，7β-羟基和7-酮衍生物及其16,16-二氘代子宫类似物。这些d2-26-羟基甾醇和[16,16-2H2]-（25R）-胆甾烯-5 -ene-3β，26-二醇（1e）是由[16,16-2H2]-（25R）-胆甾醇合成的可以由薯os皂苷元制备-5-烯-3β，26-二醇二乙酸酯（2e）。1e和2e中C-16处高度特异
• The use of prostate-specific antigen testing in the detection of localized prostate cancer. Current opinion and urological practice in the United Kingdom
  作者：A Faulkner

  DOI：10.1093/eurpub/10.4.289

  日期：2000.12.1

  Background: The prostate-specific antigen (PSA) test and its interpretation plays a crucial role in the detection of early localized prostate cancer. However, inaccuracy of the test, inability to predict the aggressiveness of the disease and the lack of evidence about the comparative effectiveness of treatments have led to major dilemmas in considering whether to employ the PSA test and which cut-off points to use in interpreting its results. The aim of this study was to evaluate current urological practice in the UK regarding the use of PSA testing. Methods: A postal questionnaire survey of all consultant urologist members of the British Association of Urological Surgeons was conducted. Statistical analysis included proportional odds regression models to examine factors associated with urologists' preferences for different definitions of ‘normal’ PSA cut-off levels. Results: The survey response rate was 60%. The majority of consultant urologists applied the PSA test routinely. There was a high level of agreement amongst UK urologists on normal PSA cut-off points (<4.0 ng/ml) for asymptomatic men under 60 years of age. There was very wide variation in the definition of normal PSA cut-offs for older (≥60 years) asymptomatic men. A preference for lower cut-off points, leading to investigation with ultrasound and biopsy, was significantly associated with larger urology department size, the presence of a prostate cancer subspecialist in the department and relatively short length of specialization in urology. Conclusions: Prostate cancer screening and early detection practices and reported incidence rates of the disease are likely to be influenced by variation in urologists' interpretations of PSA. Despite increasing evidence in favour of lower PSA cut-off levels, particularly for younger men (<60 years), urologists in the UK are divided over their interpretation. Men, particularly over age 60 years, have varying chances of further investigation following PSA testing. Any trial of prostate cancer screening or treatment should take this potential variation into account. Standard protocols for PSA interpretation should be implemented.

  背景：前列腺特异性抗原（PSA）检测及其解读在早期局限性前列腺癌的检测中起着关键作用。然而，测试的不准确性、无法预测疾病的攻击性以及缺乏治疗比较有效性的证据，导致在考虑是否使用PSA测试及其结果解释中应采用哪些临界值时，出现了重大的困境。本研究的目的是评估英国当前泌尿科医生在使用PSA检测方面的实践。方法：对所有英国泌尿外科医师协会的顾问泌尿科医生进行了邮寄问卷调查。统计分析采用了比例赔率回归模型，以检查与泌尿科医生对不同“正常”PSA临界值定义的偏好相关的因素。结果：调查的回应率为60%。大多数顾问泌尿科医生常规使用PSA测试。对于60岁以下无症状男性，英国泌尿科医生对正常PSA临界值（<4.0 ng/ml）达成了较高一致性。而对于60岁及以上的无症状男性，正常PSA临界值的定义则差异很大。偏好较低临界值（导致进行超声检查和活检）与泌尿科部门规模较大、部门内存在前列腺癌专科医生以及泌尿专科资历相对较短显著相关。结论：前列腺癌筛查和早期检测实践以及该疾病的报告发病率可能受到泌尿科医生对PSA的解读差异的影响。尽管有越来越多的证据支持特别是针对年轻男性（<60岁）采用较低PSA临界值，英国的泌尿科医生在解读上存在分歧。尤其是60岁以上的男性在PSA检测后进一步检查的机会各不相同。任何前列腺癌筛查或治疗的试验应考虑这一潜在差异。应实施PSA解读的标准协议。
• 7-hydroxy-cholesterol
  申请人：WINTHROP CHEM CO INC

  公开号：US02098985A1

  公开（公告）日：1937-11-16
• 363. Studies in the sterol group. Part L. 7-substituted cholesterol derivatives and their stereochemistry (part III). 7-alkoxycholesterol derivatives
  作者：H. B. Henbest、E. R. H. Jones

  DOI：10.1039/jr9480001798

  日期：——
• First total synthesis of xestobergsterol A and active structural analogues of the xestobergsterols
  作者：Michael E Jung、Ted W Johnson

  DOI：10.1016/s0040-4020(00)01086-3

  日期：2001.2

  The novel pentacyclic polyhydroxylated sterol, xestobergsterol A la, a strong inhibitor of histamine release from rat mast cells induced by anti-IgE, has been synthesized in 24 steps and good overall yield From stigmasterol 7. The Breslow remote functionalization process has been extended to several more highly functionalized steroid derivatives, especially those with oxygen functionality in the B-ring. The key steps of the synthesis of xestobergsterol A la and its analogues, 7-deoxyxestobergsterol A Id and 16,23-seco-23-deoxyxestobergsterol A 73, are the Breslow remote functionalization of oxygenated steroids and for compounds la and Id, a novel base-catalyzed epimerization-aldol condensation of a dione to give the desired CD-cis ring structure of the xestobergsterols. Thus the known alcohol 75, prepared from stigmasterol 7, was taken to the tetraacetate 107 which was then converted via a Breslow remote functionalization into the alkene aldehyde 114 which was transformed in 5 steps to xestobergsterol A la. Testing of the synthetic materials showed that the two analogues, 7-deoxyxestobergsterol A Ib and 16,23-seco-23-deoxyxestobergsterol A 73, are also potent inhibitors of histamine release with ICS, values (IC50 500 nM and 750 nM, respectively) being only 1015 times less than that of xestobergsterol A itself (50 nM). (C) 2001 Elsevier Science Ltd. All rights reserved.