5beta-胆烷酸-3alpha,7alpha,12alpha-三醇乙酯 | 47676-48-2

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 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
• 中文名称: 5beta-胆烷酸-3alpha,7alpha,12alpha-三醇乙酯
• 英文名称: ethyl iso-allocholate
• 英文别名: ethyl cholate；ethyl (4R)-4-[(3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3,7,12-trihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoate
• CAS: 47676-48-2
• 化学式: C₂₆H₄₄O₅
• 分子量: 436.632
• InChiKey: FPDXMWHJGOCDQJ-HZAMXZRMSA-N

物化性质

• 熔点：
  218-220 °C
• 沸点：
  552.5±50.0 °C(Predicted)
• 密度：
  1.129±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  87
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5beta-胆烷酸-3alpha,7alpha,12alpha-三醇乙酯 在 4-二甲氨基吡啶 氢氧化钾 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 0.24h， 生成 N-(3Alpha,7Alpha,12Alpha)三羟基-5β-胆甾烷-24-酰基牛黄酸
  参考文献：
  名称：

  Chemical modifications of bile acids under high-intensity ultrasound or microwave irradiation

  摘要：

  High-intensity ultrasound (HIU) and microwave (MW) irradiation, having emerged as effective promoters of organic reactions, were exploited for the synthesis of bile acids derivatives. Esterification, amidation, hydrolysis, oxidation, and reduction were investigated. Compared to conventional methods, both techniques proved much more efficient, increasing product yields and dramatically cutting down reaction times. Scaled-up studies are now under way. (C) 2004 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2004.09.007
• 作为产物：
  描述：

  3,12-dioxo-5β-cholanoic acid-(24)-ethyl ester 在 palladium on activated charcoal 、 氢气 、 溴 、 四氯苯醌 、 溶剂黄146 、 lithium tri-t-butoxyaluminum hydride 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 吡啶 、 二氯甲烷 、 甲苯 为溶剂， 150.0 ℃ 、344.75 kPa 条件下， 反应 73.0h， 生成 5beta-胆烷酸-3alpha,7alpha,12alpha-三醇乙酯
  参考文献：
  名称：

  [EN] METHODS FOR PREPARING BILE ACIDS
  [FR] PROCÉDÉS DE PRÉPARATION D'ACIDES BILIAIRES

  摘要：

  本公开提供了制备胆酸、去氧胆酸或烯醇去氧胆酸、其酯或药用或化妆品可接受的盐的方法，以及新颖且有用的合成中间体，例如，如方法1、1A、1B、2、3、3A和4所述。该方法可以以植物源类固醇作为起始物质开始，例如脱氢表雄酮（DHEA）或乙酰脱氢表雄酮（Ac-DHEA）。还提供了包含胆酸、去氧胆酸或烯醇去氧胆酸、其酯或药用或化妆品可接受的盐中的一种或多种的药用或化妆品组合物和用途，其具有高纯度，例如，不含动物来源杂质。

  公开号：

  WO2019024920A1

文献信息

• Oral Delivery of Cholic Acid-Derived Amphiphile Helps in Combating <i>Salmonella</i>-Mediated Gut Infection and Inflammation
  作者：Kavita Yadav、Prabhu Srinivas Yavvari、Sanjay Pal、Sandeep Kumar、Deepakkumar Mishra、Siddhi Gupta、Madhurima Mitra、Vijay Soni、Neha Khare、Priyanka Sharma、Chittur V. Srikanth、Arti Kapil、Archana Singh、Vinay Kumar Nandicoori、Avinash Bajaj

  DOI：10.1021/acs.bioconjchem.8b00880

  日期：2019.3.20

  A major impediment to developing effective antimicrobials against Gram-negative bacteria like Salmonella is the ability of the bacteria to develop resistance against existing antibiotics and the inability of the antimicrobials to clear the intracellular bacteria residing in the gastrointestinal tract. As the critical balance of charge and hydrophobicity is required for effective membrane-targeting antimicrobials without causing any toxicity to mammalian cells, herein we report the synthesis and antibacterial properties of cholic acid-derived amphiphiles conjugated with alkyl chains of varied hydrophobicity. Relative to other hydrophobic counterparts, a compound with hexyl chain (6) acted as an effective antimicrobial against different Gram-negative bacteria. Apart from its ability to permeate the outer and inner membranes of bacteria; compound 6 can cross the cellular and lysosomal barriers of epithelial cells and macrophages and kill the facultative intracellular bacteria without disrupting the mammalian cell membranes. Oral delivery of compound 6 was able to clear the Salmonella-mediated gut infection and inflammation, and was able to combat persistent, stationary, and multi-drug-resistant clinical strains. Therefore, our study reveals the ability of cholic acid-derived amphiphiles to clear intracellular bacteria and Salmonella-mediated gut infection and inflammation.

  开发有效的抗革兰氏阴性细菌（如沙门氏菌）抗菌药物的主要障碍是这些细菌能够对现有抗生素产生耐药性，以及抗微生物药物无法清除肠道内的细菌。由于有效的膜靶向抗微生物药物需要在不对哺乳动物细胞造成毒性的情况下，维持电荷和疏水性的关键平衡，因此我们在此报告了合成的胆酸衍生的两亲分子，这些分子与具有不同疏水性的烷基链结合。与其他疏水性相对物相比，具有己基链（6）的化合物对不同的革兰氏阴性细菌表现出有效的抗菌作用。除了能够渗透细菌的外膜和内膜之外，化合物6还可以穿越上皮细胞和巨噬细胞的细胞和溶酶体屏障，杀死兼性细胞内细菌，而不会破坏哺乳动物细胞膜。化合物6的口服投递能够清除沙门氏菌引起的肠道感染和炎症，并且能够抵抗持续、静止及多药耐药的临床菌株。因此，我们的研究揭示了胆酸衍生的两亲分子清除细胞内细菌以及沙门氏菌引起的肠道感染和炎症的能力。
• Regio- and stereoselective reductions of dehydrocholic acid
  作者：Giancarlo Cravotto、Arianna Binello、Luisa Boffa、Ornelio Rosati、Marco Boccalini、Stefano Chimichi

  DOI：10.1016/j.steroids.2006.01.004

  日期：2006.6

  12-diketo-5 beta-cholan-24-oic acid (7,12-diketolithocolic acid) as the main product. A number of different chemical reductions were carried out on DHCA; among them hydrogenation with Raney Nickel in water under high-intensity ultrasound proved highly regio- and stereoselective, yielding 7,12-diketolithocolic acid exclusively. (1)H and (13)C resonances were assigned in details thanks to a series of 1D and 2D

  脱氢胆酸 (DHCA) 是一种非天然胆汁酸，由胆酸氧化制成。据报道，它通过两种担子菌（Trametes hirsuta 和 Collybia velutipes）进行生物转化。这些菌丝体对底物和攻击选择性表现出不同的亲和力：T. hirsuta 特别是区域选择性和立体选择性还原 3-keto 基团以产生 3 alpha-hydroxy-7,12-diketo-5 beta-cholan-24-oic acid (7,12-diketolithocolic acid) 为主要产品。对 DHCA 进行了许多不同的化学还原；其中，在高强度超声下与雷尼镍在水中的氢化证明具有高度的区域和立体选择性，仅产生 7,12-二酮基乙醇酸。由于一系列 1D 和 2D NMR 运行，包括 DEPT、NOESY、HH COSY、gHSQC 和 gHMBC，详细指定了 (1)H 和 (13)C 共振。
• New cholic acid derivatives: Biocatalytic synthesis and molecular docking study
  作者：M. Antonela Zígolo、Guadalupe García Liñares、Alicia Baldessari

  DOI：10.1016/j.steroids.2015.12.014

  日期：2016.3

  derivatives of cholic acid, eight of them new compounds, were obtained through regioselective lipase-catalyzed reactions in very good to excellent yield. The influence of various reaction parameters in the enzymatic esterification, acetylation and alcoholysis reactions, such as enzyme source, alcohol or acylating agent: substrate ratio, enzyme: substrate ratio, solvent and temperature, was studied. Moreover

  通过酶催化合成了一系列胆酸衍生物。通过区域选择性脂肪酶催化的反应获得了十一种胆酸的乙酰基和酯衍生物，其中八种是新化合物，收率非常好至极佳。研究了各种反应参数对酶促酯化，乙酰化和醇解反应的影响，例如酶源，醇或酰化剂：底物比例，酶：底物比例，溶剂和温度。此外，为了阐明在酶促反应中胆酸的行为，进行了脂肪酶与胆酸和一些衍生物的分子对接。
• Synthesis and antimicrobial activity of cholic acid hydrazone analogues
  作者：Anas J.M. Rasras、Taleb H. Al-Tel、Amal F. Al-Aboudi、Raed A. Al-Qawasmeh

  DOI：10.1016/j.ejmech.2010.02.006

  日期：2010.6

  Synthesis and antimicrobial activity of cholic acid analogues 4a–t are reported. The synthesis of 4a–t was accomplished from ethylcholate 2. The hydrazone moiety was introduced via coupling of the cholic acide hydrazide (3) with appropriately functionalized aldehyde utilizing acetic acid as a catalyst. Quiet of interest in relation to the synthesized hydrazones is the formation of two rotamers s-cis

  报道了胆酸类似物4a – t的合成和抗菌活性。4a–t的合成是由胆酸乙酯2完成的。通过使用乙酸作为催化剂，通过使胆酸酰肼（3）与适当官能化的醛偶联来引入部分。与合成的azo有关的安静的是两个旋转异构体s-顺式E和s-反式E的形成。与头孢克洛和头孢克肟相比，大多数化合物对革兰氏阳性细菌显示出更强的抗菌活性。化合物4d，4i和4j表明与头孢克洛和头孢克肟相比，对粪肠杆菌的抗菌活性强15倍。某些合成的化合物（例如4a，4c，4d，4i和4l）相对于头孢克肟的抗大肠杆菌活性降低了两倍。
• Reducing Risk of Contracting Clostridium-Difficile Associated Disease
  申请人：The Regents of the Nevada System of Higher Education on behalf of the University of Neveda

  公开号：US20140045808A1

  公开（公告）日：2014-02-13

  A method of treating a patient to reduce risk of developing Clostridium difficile -associated disease or reducing existing Clostridium difficile -associated disease in a mammalian subject involves administering to a mammalian subject an effective amount of a germination-inhibiting compound derived from taurocholate. Novel compounds of this class are also provided.

  治疗患者以减少发生梭菌类难辨梭菌相关疾病的风险或减少哺乳动物主体中已存在的梭菌类难辨梭菌相关疾病的方法涉及向哺乳动物主体投入源自牛磺胆酸的抑制萌发化合物的有效量。此类新颖化合物也提供。