12α-hydroxy-3-oxochol-4-en-24-oic acid | 13073-08-0

• 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: 12α-hydroxy-3-oxochol-4-en-24-oic acid
• 英文别名: 3-oxo-12α-hydroxy-4-cholen-24-oic acid；12α-hydroxy-3-oxo-cholen-(4)-oic acid-(24)；12α-Hydroxy-3-oxo-cholen-(4)-saeure-(24)；12α-Hydroxy-3-oxo-Δ⁴-cholensaeure；12alpha-Hydroxy-3-oxochol-4-en-24-oic Acid；(4R)-4-[(8R,9S,10R,12S,13R,14S,17R)-12-hydroxy-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl]pentanoic acid
• CAS: 13073-08-0
• 化学式: C₂₄H₃₆O₄
• 分子量: 388.547
• InChiKey: BGHDKUPKUZDVRW-QUPGBHKMSA-N

物化性质

• 沸点：
  564.3±50.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  12α-hydroxy-3-oxochol-4-en-24-oic acid 在 N-甲基吗啉 、 2,6-二甲基吡啶 、 盐酸 、 lithium aluminium tetrahydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 1,2-二氯乙烷 、 苯 为溶剂， 反应 66.75h， 生成 12α-[[(tert-butyl)dimethylsilyl]oxy]cholesta-5,24-diene-3-one
  参考文献：
  名称：

  Synthesis and in vitro biological activity of 4α-(2-propenyl)-5α-cholest-24-en-3α,12α-diol, a 12α-hydroxyl analog of 4α-(2-propenyl)-5α-cholest-24-en-3α-ol: The latter is a potent activator of the low-density lipoprotein receptor promoter

  摘要：

  4 alpha-(2-Propenyl)-5 alpha-cholest-24-en-3 alpha-ol (3) was shown recently in a Chinese hamster ovary (CHO) cell-based low-density lipoprotein receptor/luciferase (LDLR/Luc) assay to be a potent transcriptional activator of the LDL receptor promoter in the presence of 25-hydroxycholesterol. Because of the involvement of 12 alpha-hydroxylation in the metabolism of cholesterol, we are interested in investigating the effect of introducing a 12 alpha-hydroxyl group to 3 on the transcriptional activity of the LDL receptor promoter. Thus 4 alpha-(2-propenyl)-5 alpha-cholest-24-en-3 alpha,12 alpha-diol (14), a 12 alpha-hydroxyl analog of 3, was synthesized from deoxycholic acid via the formation of 12 alpha-[[(tert-butyl)dimethylsilyl]oxy]-4 alpha-(2-propenyl (11). Test results show that 14 is inactive at concentrations of up to 20 mu g/ml, compared to 3 with an EC30 value of 2.6 mu M, in the CHO cell-based LDLR/Lac assay. Apparently introduction of a 12 alpha-hydroxyl group abolishes the capability of 3 alpha-sterol 14 to activate the transcription of the LDL receptor promoter. However, in the [1-(14)Cacetate]cholesterol biosynthesis inhibition assay in CHO cells, 14 at 10 mu g/ml (23 mu M) is shown to inhibit the cholesterol biosynthesis by 51% relative to the control cells. Our previous studies indicated that 3 showed a 38% inhibition, but 4 alpha-(2-propenyl)-5 alpha-cholestan-3 alpha-ol (1) exhibited no inhibition in the same assay at 10 mu g/ml. In summary the results indicate that, in addition to the 24,25-unsaturation, the 12 alpha-hydroxyl group in 14 has also conferred an inhibitory effect on cholesterol biosynthesis in CHO cells; however, the inhibition of cholesterol biosynthesis by 14 does not lead to the transcriptional activation of the LDL receptor promoter. (C) 1999 Published by Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(99)00053-7
• 作为产物：
  描述：

  12α-acetoxy-3-oxo-cholen-(4)-oic acid-(24) 在 氢氧化钾 作用下， 生成 12α-hydroxy-3-oxochol-4-en-24-oic acid
  参考文献：
  名称：

  Matsumoto, Journal of Biochemistry, 1944, vol. 36, p. 183,189

  摘要：

  DOI：

文献信息

• Synthetic approaches to steroidal alkaloids II. Preparation and reactions of 12-oxo-dinorcholanic acids
  作者：J.W. Huffman、R.R. Sobti

  DOI：10.1016/s0039-128x(70)80153-2

  日期：1970.7

  acid (I) to a 5 α -C-nor-D-homo-dinorcholan-22-oic acid (III) are described. Reaction of the diacetate of I with lead tetraacetate, gave 3 α, 12 α -diacetoxy-24-nor-5 β -chol-22-ene (VIII), which on periodate-permanganate oxidation afforded diactoxybisnordeoxycholic acid (IX). The olefin (VIII) was also obtained from I by a Curtius reaction, followed by methylation and Hofmann elimination. The stereochemistry

  摘要 在藜芦生物碱的合成方法中，描述了将脱氧胆酸 (I) 转化为 5 α -C-nor-D-homo-dinorcholan-22-oic 酸 (III) 的实验。I 的二乙酸酯与四乙酸铅反应，得到 3 α, 12 α -diacetoxy-24-nor-5 β -chol-22-ene (VIII)，其在高锰酸盐-高锰酸盐氧化中得到二乙酰氧基双去氧胆酸 (IX)。烯烃(VIII)也通过Curtius反应从I获得，随后进行甲基化和霍夫曼消除。该系列中 C-5 的立体化学通过用溴处理 3-oxo-12 α -acetoxy-23,24-dinor-5 β -cholan-22-oic acid (XI)，然后脱卤化氢，金属氨还原而反转和硼氢化钠还原得到双去氧胆酸的 5 α-异构体 (XIII)。衍生自 XII 和 XIII 的 12-酮的甲苯磺酰腙进行 Bamford-Stevens 反应，
• Biotransformations of Bile Acids with Bacteria from Cayambe Slaughterhouse (Ecuador): Synthesis of Bendigoles
  作者：Stefania Costa、Maria Elena Maldonado Rodriguez、Irene Rugiero、Morena De Bastiani、Alessandro Medici、Elena Tamburini、Paola Pedrini

  DOI：10.1002/cbdv.201500300

  日期：2016.8

  The biotransformations of cholic acid (1a), deoxycholic acid (1b), and hyodeoxycholic acid (1c) to bendigoles and other metabolites with bacteria isolated from the rural slaughterhouse of Cayambe (Pichincha Province, Ecuador) were reported. The more active strains were characterized, and belong to the genera Pseudomonas and Rhodococcus. Various biotransformation products were obtained depending on

  据报道，胆酸 (1a)、脱氧胆酸 (1b) 和猪脱氧胆酸 (1c) 被从卡扬贝农村屠宰场（厄瓜多尔皮钦查省）分离出的细菌转化为苯菌灵和其他代谢物。更活跃的菌株被表征，属于假单胞菌属和红球菌属。根据细菌和底物获得各种生物转化产物。胆酸 (1a) 与 P. mendocina ECS10、3,12-dioxo-4-ene 衍生物 4a 一起提供了 3-oxo 和 3-oxo-4-ene 衍生物 2a 和 3a（分别为 45% 和 45%）（ 60%) 与 Rh。erythropolis ECS25 和 9,10-secosteroid 6 (15%) 与 Rh。红城 ECS12。Bendigole F (5a) 以 20% 的比例用 P. fragi ECS22 获得。脱氧胆酸 (1b) 与 P. prosekii ECS1 和 Rh 生成 3-氧代衍生物 2b。erythropolis ECS25（分别为
• Improved synthesis of 3-keto, 4-ene-3-keto, and 4,6-diene-3-keto bile acids
  作者：Raymond A. Leppik

  DOI：10.1016/0039-128x(83)90087-9

  日期：1983.4

  Cholic and deoxycholic acids can be converted into 3-keto derivatives in 75-80% yield, by a four-step synthesis consisting of formylation, selective deformylation of the 3-formoxyl group, oxidation, then deformylation of the remaining formoxyl groups. The intermediate 3-keto formoxyl acids in this sequence were shown to be suitable starting compounds for the synthesis of 4-ene-3-keto acids, in 55-60% yield, via bromination, dehydrobromination, and deformylation. By extending the dehydrobromination reaction, the 7 alpha-formoxyl group of the intermediate 4-ene-3-keto-7 alpha,12 alpha-diformoxyl acid is also lost, hence providing a useful synthetic route to 4,6-diene-3-keto bile acids.
• Mori,H. et al., Chemical and pharmaceutical bulletin, 1962, vol. 10, # 9, p. 842 - 851
  作者：Mori,H. et al.

  DOI：——

  日期：——
• Über Gallensäuren und verwandte Stoffe. 14. Mitteilung. 3-Keto-cholen-(11)-säure und 3-Keto-choladien-(4,11)-säure
  作者：V. Burckhardt、T. Reichstein

  DOI：10.1002/hlca.19420250505

  日期：1942.8.1