5α-bromo-3β-acetoxyl-6β-hydroxyl-cholest-24-one | 325458-96-6

• 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: 5α-bromo-3β-acetoxyl-6β-hydroxyl-cholest-24-one
• 英文别名: 3β-acetoxy-5α-bromo-6β-hydroxycholestan-24-one；3β-acetoxy-5α-bromocholestan-6β-ol-24-one；3β-acetoxy-5a-bromo-6β-hydroxycholestane-24-one；[(3S,5R,6R,8S,9S,10R,13R,14S,17R)-5-bromo-6-hydroxy-10,13-dimethyl-17-[(2R)-6-methyl-5-oxoheptan-2-yl]-1,2,3,4,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-yl] acetate
• CAS: 325458-96-6
• 化学式: C₂₉H₄₇BrO₄
• 分子量: 539.594
• InChiKey: MFNOFYXHHOFXKG-FAXQMJRSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5α-bromo-3β-acetoxyl-6β-hydroxyl-cholest-24-one 在 碘苯二乙酸 、 硫酸 、 碘 、 sodium carbonate 、 溶剂黄146 、 间氯过氧苯甲酸 、 锌 作用下， 以 二氯甲烷 、 环己烷 、 水 、 丙酮 、 苯 为溶剂， 反应 48.83h， 生成 3β,5α,6β,19-tetrahydroxycholestan-24-one
  参考文献：
  名称：

  Naturally occurring marine steroid 24-methylenecholestane-3β,5α,6β,19-tetraol functions as a novel neuroprotectant

  摘要：

  Steroids have been shown to have multiple effects on the nervous system including neuroprotective activities, and they have the potential to be used for the treatment of neurodegenerative diseases. In this current study, we tested the hypothesis that the marine steroid 24-methylenecholestane-3 beta,5 alpha,6 beta,19-tetraol (Tetrol) has a neuroprotective effect. (1) We synthesized Tetrol through a multiple step reaction starting from hyodeoxycholic acid (HDCA). (2) We then evaluated the neuroprotective effect of Tetrol with a glutamate-induced neuronal injury model in vitro. Tetrol concentration dependently increased the survival rate of cerebellar granule neurons challenged with toxic concentration of glutamate. Consistently, Tetrol significantly decreased glutamate-induced lactate dehydrogenase (LDH) release with a threshold concentration of 2.5 mu M. (3) We further evaluated the neuroprotective effect of Tetrol in a middle cerebral artery occlusion (MCAO)-induced cerebral ischemia model in rat. Tetrol, at a dose of 12 mg/kg, significantly decreased MCAO-induced infarction volume by similar to 50%. (4) Finally, we probed the mechanism and found that Tetrol concentration dependently attenuated N-methyl-D-aspartate (NMDA)-induced intracellular calcium ([Ca2+](i)) increase with an IC50 of 7.8 +/- 0.62 mu M, and inhibited NMDA currents in cortical neurons with an IC50 of 10.28 +/- 0.71 mu M. Taken together, we have synthesized and characterized Tetrol as a novel neuroprotectant through negative modulation of NMDA receptors. (C) 2015 Published by Elsevier Inc.

  DOI：

  10.1016/j.steroids.2015.11.005
• 作为产物：
  描述：

  (3β)-3-(acetyloxy)chol-5-en-24-oyl chloride 在 N-溴代丁二酰亚胺(NBS) 、 高氯酸 、 sodium thiosulfate 、 magnesium 作用下， 以 四氢呋喃 、 乙醚 、 水 为溶剂， 反应 4.08h， 生成 5α-bromo-3β-acetoxyl-6β-hydroxyl-cholest-24-one
  参考文献：
  名称：

  Naturally occurring marine steroid 24-methylenecholestane-3β,5α,6β,19-tetraol functions as a novel neuroprotectant

  摘要：

  Steroids have been shown to have multiple effects on the nervous system including neuroprotective activities, and they have the potential to be used for the treatment of neurodegenerative diseases. In this current study, we tested the hypothesis that the marine steroid 24-methylenecholestane-3 beta,5 alpha,6 beta,19-tetraol (Tetrol) has a neuroprotective effect. (1) We synthesized Tetrol through a multiple step reaction starting from hyodeoxycholic acid (HDCA). (2) We then evaluated the neuroprotective effect of Tetrol with a glutamate-induced neuronal injury model in vitro. Tetrol concentration dependently increased the survival rate of cerebellar granule neurons challenged with toxic concentration of glutamate. Consistently, Tetrol significantly decreased glutamate-induced lactate dehydrogenase (LDH) release with a threshold concentration of 2.5 mu M. (3) We further evaluated the neuroprotective effect of Tetrol in a middle cerebral artery occlusion (MCAO)-induced cerebral ischemia model in rat. Tetrol, at a dose of 12 mg/kg, significantly decreased MCAO-induced infarction volume by similar to 50%. (4) Finally, we probed the mechanism and found that Tetrol concentration dependently attenuated N-methyl-D-aspartate (NMDA)-induced intracellular calcium ([Ca2+](i)) increase with an IC50 of 7.8 +/- 0.62 mu M, and inhibited NMDA currents in cortical neurons with an IC50 of 10.28 +/- 0.71 mu M. Taken together, we have synthesized and characterized Tetrol as a novel neuroprotectant through negative modulation of NMDA receptors. (C) 2015 Published by Elsevier Inc.

  DOI：

  10.1016/j.steroids.2015.11.005

文献信息

• Design and synthesis of polyhydroxy steroids as selective inhibitors against AKR1B10 and molecular docking
  作者：Wenli Chen、Xinying Chen、Shujia Zhou、Hong Zhang、Ling Wang、Jun Xu、Xiaopeng Hu、Wei Yin、Guangmei Yan、Jingxia Zhang

  DOI：10.1016/j.steroids.2016.03.004

  日期：2016.6

  AKR1B10 is a member of the human aldo-keto reductase superfamily which is highly expressed in several types of cancers, and has been regarded as a promising cancer therapeutic target. In this paper, a series of polyhydroxy steroids were designed and synthesized to selectively inhibit AKR1B10 activity. The most selective compound, novel compound 6, has an IC50 of 0.83 +/- 0.07 mu M and a selectivity of more than 120-fold for AKR1B10/AKR1B1. Structure-activity relation analyses indicate that hydroxyl at C-19 can significantly improve the selective inhibition of AKR1B10. The binding mode of AKR1B10 and its inhibitors were studied. (C) 2016 Published by Elsevier Inc.
• Synthesis of polyhydroxysterols (I): synthesis of 24-methylenecholest-4-en-3β,6β-diol, a cytotoxic natural hydroxylated sterol
  作者：JianGuo Cui、LongMei Zeng、JingYu Su、WeiGang Lu

  DOI：10.1016/s0039-128x(00)00132-x

  日期：2001.1

  Starting from stigmasterol (2), 24-methylenecholest-4-en-3 beta ,6 beta -diol (1), a cytotoxic natural dihydroxylated sterol, was synthesized via 10 steps in 20% overall yield. The introduction of a side-chain of sterol was achieved by solid-liquid phase-transfer Wittig reaction using (3-methyl-2-oxo)butyltriphenylarsonium bromide (12) and K2CO3. Construction of the steroidal nucleus was finished by the addition of 3 beta -acetoxycholest-5,6-en-24-one (7) with NBA in dioxane under ambient temperature and by the elimination of 3 beta, 6 beta -diacetoxy-5a-bromocholestane-24-one (9). The spectral data of the synthetic product (1) are completely consistent with those of the natural compound (1). (C) 2001 Elsevier Science Inc. All rights reserved.
• Synthesis of polyhydroxysterols (IV): synthesis of 24-methylene-cholesta-3β,5α,6β,19-tetrol, a cytotoxic natural hydroxylated sterol
  作者：Weigang Lu、Longmei Zeng、Jingyu Su

  DOI：10.1016/j.steroids.2004.04.002

  日期：2004.7

  The cytotoxic, polyhydroxylated sterol 24-methylene-cholesta-3beta,5alpha,6beta,19-tetrol (1), previously isolated from the soft corals Nephthea albida and N. tiexieral verseveldt, was synthesized using stigmasterol as the starting material by 10 steps in 9% overall yield. The spectral data and physical constants of 1 were identical with those of the natural product. This is the first report of the synthesis of 1. (C) 2004 Elsevier Inc. All rights reserved.