5β cholene-1, one-3, oate-24 de methyle | 91667-86-6

• 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: 5β cholene-1, one-3, oate-24 de methyle
• 英文别名: methyl bromo-3-oxo-5β-chol-1-en-24-oate；methyl 3-oxo-5β-chol-1-en-24-oate；methyl (4R)-4-[(5R,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl]pentanoate
• CAS: 91667-86-6
• 化学式: C₂₅H₃₈O₃
• 分子量: 386.575
• InChiKey: OFWBYWLBFPBYTD-NAMNPDSASA-N

物化性质

• 沸点：
  477.0±14.0 °C(Predicted)
• 密度：
  1.047±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5β cholene-1, one-3, oate-24 de methyle 在 potassium tert-butylate 、 水 、 sodium hydroxide 作用下， 生成 3-Oxo-4.4-dimethyl-chol-5-en-24-saeure
  参考文献：
  名称：

  Synthesis and biological evaluation of 4,4-dimethyl lithocholic acid derivatives as novel inhibitors of protein tyrosine phosphatase 1B

  摘要：

  Protein tyrosine phosphatase 1B (PTP1B) is a major negative regulator of both insulin and leptin signals. For years, inhibiting of PTP1B has been considered to be a potential therapeutics for treating Type 2 diabetes and obesity. Recently, we recognized lithocholic acid (LCA) as a natural inhibitor against PTP1B (IC50 = 12.74 mu M) by a vertical screen for the first time. Further SAR research was carried out by synthesizing and evaluating a series of compounds bearing two methyls at C-4 position and a fused heterocycle to ring A. Among them, compound 14b achieved a PTP1B inhibitory activity about eightfold than LCA and a 14-fold selectivity over the homogenous enzyme TCPTP. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.040
• 作为产物：
  描述：

  25,26,27-trisnorcholesta-1,4,6-trien-3-on-24-oic acid methyl ester 在 Lindlar's catalyst sodium hydroxide 、 氢气 、 双氧水 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 苯 为溶剂， 反应 2.0h， 生成 5β cholene-1, one-3, oate-24 de methyle
  参考文献：
  名称：

  Synthesis of 1-hydroxylated bile acids: Methyl 1α, 3α-dihydroxy 5β-cholan-24-oate

  摘要：

  Methyl 1 alpha,3 alpha-dihydroxy 5 beta-cholan-24-oate was synthesized to provide a model compound for the mass spectrometric identification of 1 alpha-hydroxylated bile acids.

  DOI：

  10.1016/0039-128x(82)90006-x

文献信息

• Bile acids. LXXIX. synthesis and reduction of 1,4-dien-3-ones of various bile acids
  作者：Mohammed N. Iqbal、William H. Elliott

  DOI：10.1016/0039-128x(89)90022-6

  日期：1989.3

  bile acids (IIa-d), their methyl esters (IIe-h), and their formylated derivatives (IIi-k) were synthesized and their reduction investigated by both catalytic and chemical methods as an alternative route to the synthesis of allo bile acids. Lithium-ammonia reduction proved to be the better method for the reduction of these 1,4-dien-3-ones producing the 3-keto- and 3 beta-hydroxy-allo bile acids (Vb-d)

  合成了各种胆汁酸 (IIa-d) 的 1,4-Dien-3-ones、它们的甲酯 (IIe-h) 和它们的甲酰化衍生物 (IIi-k)，并通过催化和化学方法研究了它们的还原情况，如合成别胆汁酸的另一种途径。锂-氨还原被证明是还原这些 1,4-二烯-3-酮的更好方法，产生 3-酮-和 3-β-羟基-别胆酸 (Vb-d) 和 (VIb-d)产率为 66-72%。
• The application of dimethyldioxirane for the selective oxidation of polyfunctional steroids
  作者：Tomoaki Sasaki、Ryusei Nakamori、Takeru Yamaguchi、Yuka Kasuga、Takashi Iida、Toshio Nambara

  DOI：10.1016/s0009-3084(00)00209-7

  日期：2001.2

  Oxidation and epoxidation reactions of a series of structurally different steroids related to methyl 5 beta-cholanoates having hydroxyl groups and/or double bonds by treatment with dimethyldioxirane (DMDO) are described. Steroidal alcohols, olefines, and unsaturated alcohols and conjugated enones with DMDO were transformed into ketones, epoxides, and epoxy-ketones, respectively, in good isolated yields

  描述了通过用二甲基二环氧乙烷（DMDO）处理，与具有羟基和/或双键的5β-胆酸甲酯相关的一系列结构不同的类固醇的氧化和环氧化反应。甾烷醇，烯烃和不饱和醇以及具有DMDO的共轭烯酮分别以良好的分离收率转化为酮，环氧化物和环氧酮。还讨论了DMDO反应的区域选择性和立体选择性与有机过酸，叔丁基氢过氧化物和碱性过氧化氢所观察到的不同。
• Synthesis of the 1.BETA.-hydroxylated bile acids, unusual bile acids in human biological fluids.
  作者：MASAHIKO TOHMA、REIJIRO MAHARA、HIROMI TAKESHITA、TAKAO KUROSAWA、SHIGEO IKEGAWA

  DOI：10.1248/cpb.34.2890

  日期：——

  1β-Hydoxylated lithocholic (10a), deoxycholic (10b), chenodeoxycholic (10c) and cholic (10d) acids were synthesized from the corresponding bile acid methyl esters (1a-d) as starting materials. The Δ1-unsaturated ketones (6a, e-g) were prepard from the 3-oxo bile acid esters (2a-d) via reductive debromination of their 2, 4-dibromides (3a, e-g) with chromous acetate and dehydrobromination with lithium carbonate-lithium bromide, and oxidized with alkaline hydrogen peroxide to give the 1β-2β-epoxyketones (7a, e-g). Reductive cleavage of the epoxides (7a, e-g) and subsequent reduction with sodium borohydride afforded the 1β, 3α-dihydroxy compounds (9a, e-g), which were hydrolyzed to the 1β-hydroxylated bile acids (10a-d). 1β, 3α, 12α-Trihydroxy-5β-cholan-24-oic acid (10b) was identified in the urine of healthy men and patients with kidney disease by gas chrmatography-mass spectrometric analysis. Novel 1β, 3α, 7α-trihydroxy-(10c) and 1β, 3α, -7α, 12α-tetrahydroxy-5β-cholan-24-oic acids (10d) were detected in human meconium.

  1β-羟基胆酸（10a）、脱氧胆酸（10b）、鹅去氧胆酸（10c）和胆酸（10d）是从相应的胆酸甲酯（1a-d）作为起始原料合成的。Δ1-不饱和酮（6a、e-g）是通过用乙酸铬还原脱除其2,4-二溴化物（3a、e-g）的溴，并用碳酸锂-溴化锂脱氢，然后用碱性过氧化氢氧化，得到1β-2β-环氧酮（7a、e-g）。环氧物（7a、e-g）的还原裂解和随后的硼氢化钠还原反应得到1β,3α-二羟基化合物（9a、e-g），后者被水解为1β-羟基胆酸（10a-d）。通过气相色谱-质谱分析，在健康男性和肾脏疾病患者的尿液中鉴定出1β,3α,12α-三羟基-5β-胆烷-24-酸（10b）。在人类胎粪中检测到新的1β,3α,7α-三羟基-（10c）和1β,3α,7α,12α-
• Synthesis of the 1.BETA.-hydroxylated bile acids and identification of 1.BETA.,3.ALPHA.,7.ALPHA.-trihydroxy- and 1.BETA.,3.ALPHA.,7.ALPHA.,12.ALPHA.-tetrahydroxy-5.BETA.-cholan-24-oic acids in human meconium.
  作者：Masahiko Tohma、Reijiro Mahara、Hiromi Takeshita、Takao Kurosawa、Shigeo Ikegawa、Hiroshi Nittono

  DOI：10.1248/cpb.33.3071

  日期：——

  The 1β-hydroxylated lithocholic (1), deoxycholic (2), chenodeoxycholic (3) and cholic acids (4) were synthesized from the corresponding bile acids as starting materials. These unusual bile acids in human meconium were determined by the selected ion monitoring in gas chromatography-mass spectrometry, and novel 1β-hydroxychenodeoxycholic (3) and 1β-hydroxycholic acids (4) were identified in significant amounts of 10.6% and 5.8%, respectively, of the total bile acids.

  以相应的胆汁酸为起始原料合成1β-羟基化石胆酸(1)、脱氧胆酸(2)、鹅去氧胆酸(3)和胆酸(4)。通过气相色谱-质谱法中的选择离子监测来测定人胎便中的这些不寻常胆汁酸，并鉴定出新型 1β-羟基鹅去氧胆酸 (3) 和 1β-羟基胆酸 (4)，含量分别为 10.6% 和 5.8% ，总胆汁酸。
• 1β-HYDROXYLATION IN 5β-STEROIDS: AN EFFICIENT SYNTHESIS OF 1β,3α-DIHYDROXY-5β-CHOLAN-24-OIC ACID
  作者：Takeru Yamaguchi、Ryusei Nakamori、Takashi Iida、Toshio Nambara

  DOI：10.1081/scc-100104006

  日期：2001.1.1

  of lithocholic acid (3α-hydroxy-5β-cholan-24-oic acid) to 1β,3α-dihydroxy-5β-cholan-24-oic acid. The key reactions used are regioselective functionalization at C-2 in the 5β-steroid nucleus, stereoselective epoxidation of intermediary α,β-conjugated ketone with dimethyldioxirane, and subsequent reductive cleavage of the resulting β-epoxy-ketone with PhSeNa.

  描述了一种在 5β-类固醇 (A/B-顺式) 中 C-1 处进行氧官能化的有效方法，例如将石胆酸 (3α-羟基-5β-cholan-24-oic 酸) 转化为 1β,3α-二羟基-5β-cholan-24-oic酸。使用的关键反应是 5β-甾体核中 C-2 处的区域选择性功能化、中间体 α,β-共轭酮与二甲基二环氧乙烷的立体选择性环氧化，以及随后用 PhSeNa 还原裂解所得 β-环氧-酮。