24-methylcholest-24(28)-ene-3β,5α,6β,19-tetraol | 142754-97-0

• 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: 24-methylcholest-24(28)-ene-3β,5α,6β,19-tetraol
• 英文别名: (3β,5α,6β)-ergost-24(28)-ene-3,5,6,19-tetrol；(3β,5α,6β)-ergost-24(28)-en-3,5,6,19-tetrol；24-methylenecholestane-3β,5α,6β,19-tetraol；24-methylene-cholest-3β,5α,6β,19-tetrol；24-methylenecholesta-3β,5α,6β,19-tetrol；(3β,5α,6β)-24-methylcholest-24(28)-ene-3,5,6,19-tetrol；(3S,5R,6R,8S,9S,10R,13R,14S,17R)-10-(hydroxymethyl)-13-methyl-17-[(2R)-6-methyl-5-methylideneheptan-2-yl]-1,2,3,4,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,5,6-triol
• CAS: 142754-97-0
• 化学式: C₂₈H₄₈O₄
• 分子量: 448.687
• InChiKey: YHXSSRWVHUDCDJ-GUNASTJBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  80.9
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  24-methylcholest-24(28)-ene-3β,5α,6β,19-tetraol 以 氘代氯仿 为溶剂， 反应 168.0h， 生成 24-methylenecholesta-6β,19-epoxy-3β,5α-diol
  参考文献：
  名称：

  Sesquiterpenoids and Artificial 19-Oxygenated Steroids from the Formosan Soft Coral Nephthea erecta

  摘要：

  Chemical investigations on the acetone and MeOH solubles of the soft coral Nephthea erecta have afforded five new sesquiterpenoids (1-5), one known sesquiterpene, kelsoene (6), and two known 19-oxygenated steroids (10 and 11). In addition, three unexpected artificial 19-oxygenated steroids (7-9) were obtained by letting 10 and 11 stand in CDCl3 for prolonged periods of time. The structures of 1-9 were elucidated by extensive spectroscopic analyses, and their cytotoxicity against selected cancer cells was measured in vitro.

  DOI：

  10.1021/np070189t
• 作为产物：
  描述：

  3B-羟基-D5-胆烯酸 在 吡啶 、 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 氯化亚砜 、 高氯酸 、 碘苯二乙酸 、 硫酸 、 碘 、 sodium carbonate 、 sodium thiosulfate 、 magnesium 、 溶剂黄146 、 间氯过氧苯甲酸 、 锌 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 环己烷 、 水 、 丙酮 、 苯 为溶剂， 反应 63.41h， 生成 24-methylcholest-24(28)-ene-3β,5α,6β,19-tetraol
  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

• THE APPLICATION OF MARINE STEROID IN PREPARING THE MEDICINE OF TREATING NEURONS DAMAGING
  申请人：Sun Yat-Sen University

  公开号：EP2047853A1

  公开（公告）日：2009-04-15

  The application of marine steroid, i.e. 24-methylene-cholest-3β,5α,6β,19-tetrol, in preparing the medicine of treating neurons damaging is provided in the present invention. The keto-sterols compounds marine steroid YC-1 extracted from Nephthea albida has the action of neuronal protection, and no toxic reaction under the effective protective dosage.

  本发明提供了海洋固醇（即 24-亚甲基-胆甾-3β,5α,6β,19-四醇）在制备治疗神经元损伤药物中的应用。从白花蛇舌草中提取的酮类甾醇化合物海洋甾体 YC-1 具有保护神经元的作用，在有效保护剂量下无毒性反应。
• 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 (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.
• [EN] METHOD FOR SYNTHESIS OF CHOLEST-3ß,5a,6ß,19-TETRAHYDROXY-24-ONE AND ITS DERIVATIVES<br/>[FR] PROCEDE DE SYNTHESE DE CHOLEST-3?,5?,6?,19-TETRAHYDROXY-24-ONE ET SES DERIVES
  申请人：UNIV SUN YAT SEN

  公开号：WO2007076655A1

  公开（公告）日：2007-07-12

  [EN] A synthesis process of cholest-3ß,5a,6ß,19-tetrahydroxy-24-one and its derivatives includes the steps of: synthesis of 3ß-acetoxy-cholest-5-en-24-acid with hyodesoxycholic acid as the starting material; synthesis of cholenic acid chloride by reaction with thionyl chloride; reaction with isopropylcadmium reagent under ultrasonic irradiation to produce 3ß-acetoxy-cholest-5-en-24-one; then reaction with N-bromosuccinimide/water solution of perchloric acid system to obtain 3ß-acetoxy-cholest-5a-bromo-6ß-hydroxy-24-one; reaction with diacetoxy iodobenzene to give 3ß-acetoxy-cholest-5a-bromo-6ß,19-epoxy-24-one; reduction with Zn powder/glacial acetic acid system to give 3ß,19-diacetoxy-cholest-5-en-24-one; oxidation of the double bond at position 5 and 6; then hydrolysis to produce cholest-3ß,5a,6ß,19-tetrahydroxy-24-one; finally reaction with methyltriphenylphosphonium bromide to produce 24-methylene-cholest-3ß,5a,6ß,19-tetraol; and reaction with hydrazine to give cholest-3ß,5a,6ß,19-tetrahydroxy-24-dihydrazone. The synthesis process according to the invention has the characteristic of lower price, material availability, scientific and reasonable synthetic routes, higher yield, and the like. The target compounds have significantly protective effect on neuronal apoptosis evoked by low K⁺.
  [FR] Un procédé de synthèse de cholest-3ß,5a,6ß,19-tétrahydroxy-24-one et ses dérivés, lequel procédé comprend: la synthèse de l'acide 3ß-acétoxy-cholest-5-en-24 avec l'acide hyodésoxycholique tenant lieu de matière première; la synthèse de chlorure d'acide cholénique par réaction avec un chlorure thionyle; la réaction avec un réactif d'isopropylcadmium sous l'effet d'un rayonnement ultrasonore afin d'obtenir 3ß-acetoxy-cholest-5-en-24-one; la réaction avec une solution de N-bromosuccinimide/eau du système d'acide perchlorique afin d'obtenir 3ß-acétoxy-cholest-5a-bromo-6ß-hydroxy-24-one; la réaction avec un diacétoxy iodobenzène afin d'obtenir 3ß-acétoxy-cholest-5a-bromo-6ß,19-époxy-24-one; la réduction avec un système d'acide acétique Zn poudre/glacial afin d'obtenir 3ß,19-diacétoxy-cholest-5-en-24-one; l'oxydation de la double liaison en position 5 et 6; l'hydrolyse afin d'obtenir cholest-3ß,5a,6ß,19-tétrahydroxy-24-one; la réaction avec un bromure de méthyltriphénylphosphonium afin d'obtenir 24-méthylène-cholest-3ß,5a,6ß,19-tétraol; et finalement la réaction avec une hydrazine afin d'obtenir cholest-3ß,5a,6ß,19-tétrahydroxy-24-dihydrazone. Le procédé de synthèse de cette invention est caractérisé par un prix inférieur, une meilleure disponibilité des matières premières, une application synthétique viable et un bon rendement, entre autres. Les composés de cette invention ont un effet hautement protecteur contre l'apoptose neuronale induite par une faible teneur de K+.
• [EN] THE APPLICATION OF MARINE STEROID IN PREPARING THE MEDICINE OF TREATING NEURONS DAMAGING<br/>[FR] UTILISATION DE STÉROÏDE MARIN DANS LA PRÉPARATION D'UN MÉDICAMENT POUR LE TRAITEMENT DES LÉSIONS NEURONALES
  申请人：UNIV SUN YAT SEN

  公开号：WO2008017216A1

  公开（公告）日：2008-02-14

  [EN] The application of marine steroid, i.e. 24-methylene-cholest-3ß,5a,6ß,19-tetrol, in preparing the medicine of treating neurons damaging is provided in the present invention. The keto-sterols compounds marine steroid YC-1 extracted from Nephthea albida has the action of neuronal protection, and no toxic reaction under the effective protective dosage.
  [FR] La présente invention concerne l'utilisation de stéroïde marin, c'est-à-dire cholest-3ß,5a,6ß,19-tétraol(24-méthylène), dans la préparation d'un médicament destiné au traitement des lésions neuronales. Le stéroïde marin YC-1 des composés cétostérols extrait de Nephthea albida possède une propriété de protection neuronale et ne provoque aucune réaction toxique au dosage protecteur efficace.