acetyllithocholic acid | 4057-84-5

• 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: acetyllithocholic acid
• 英文别名: 3α-acetoxy-5β-cholan-24-oic acid；3α-acetyloxy-5β-cholan-24-oic acid；lithocholic acid acetate；(R)-4-((3R,5R,8R,9S,10S,13R,14S,17R)-3-acetoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid；3-acetyllithocholic acid；(4R)-4-[(3R,5R,8R,9S,10S,13R,14S,17R)-3-acetyloxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid
• CAS: 4057-84-5
• 化学式: C₂₆H₄₂O₄
• 分子量: 418.617
• InChiKey: FCQRLHQHKFKTQE-HCTDMSSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.923
• 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：

  acetyllithocholic acid 在 吡啶 、 periodic acid dihydrate 、 氧气 、 copper diacetate 、 lead(IV) tetraacetate 、 rose bengal 、 碳酸氢钠 、 间氯过氧苯甲酸 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 苯 为溶剂， 反应 28.0h， 生成 孕烷醇酮
  参考文献：
  名称：

  Bile Acid-Based 1,2,4-Trioxanes: Synthesis and Antimalarial Assessment

  摘要：

  A new series of bile acid-based trioxanes 23a-d, 24a-d, 25a-d, 26a, 26b, and 26d have been synthesized and assessed for their antimalarial activity against multidrug-resistant Plasmodium yoelii in Swiss mice by oral route. The antimalarial activity of these trioxanes showed a strong dependence on the side-chain length; shortening side-chain length lead to increase in activity. The antimalarial activity also showed even stronger dependence on the stereochemistry at C3 and C6 (C21 in Figure 5) of the trioxane moiety. Of the two diastereomers isolated of each of the trioxanes, more polar one was significantly more active than the less polar one. The more polar diastereomer of the trioxanes 26a, 26b, and 26d, were the most active compounds of the series. All these three trioxanes provided 100% protection at 24 mg/kg X 4 days. In this model beta-arteether provided 100% and 20% protection at 48 mg/kg X 4 days and 24 mg/kg X 4 days, respectively.

  DOI：

  10.1021/jm301323k
• 作为产物：
  描述：

  石胆酸 、 乙酰氯 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 1.0h， 以95%的产率得到acetyllithocholic acid
  参考文献：
  名称：

  维生素D受体介导的胆固醇和维生素D代谢产物的合成和评估

  摘要：

  对胆固醇和维生素D的第一阶段和第二阶段代谢产物进行了系统研究，以确定它们的生物学活性是否由维生素D受体（VDR）介导。这项研究有必要开发新的合成方法，以合成石胆酸（LCA）葡糖醛酸内酯（Gluc）。生化和基于细胞的测定法被用来证明羟基化的LCA类似物不能结合VDR。这排除了VDR介导其生物学和药理活性。在合成的LCA缀合物中，鉴定了一种新型的VDR激动剂。LCA Gluc II增加了CY14524A1在DU145癌细胞中的表达，特别是在存在内源性VDR配体1,25（OH）2 D 3的情况下。此外，LCA的甲酯被鉴定为新型VDR拮抗剂。首次，我们证明了假定的维生素D最终无活性代谢产物钙柠檬酸比胆汁酸LCA具有更高的活化VDR介导的转录的能力。由于与维生素D相比具有更高的代谢稳定性，极低的毒性以及胆汁和肠中的高浓度，钙柠檬酸可能是维生素D对结肠癌的保护作用的重要介体。

  DOI：

  10.1016/j.ejmech.2016.01.002

文献信息

• Chemoselective Boron-Catalyzed Nucleophilic Activation of Carboxylic Acids for Mannich-Type Reactions
  作者：Yuya Morita、Tomohiro Yamamoto、Hideoki Nagai、Yohei Shimizu、Motomu Kanai

  DOI：10.1021/jacs.5b04175

  日期：2015.6.10

  The carboxyl group (COOH) is an omnipresent functional group in organic molecules, and its direct catalytic activation represents an attractive synthetic method. Herein, we describe the first example of a direct catalytic nucleophilic activation of carboxylic acids with BH3·SMe2, after which the acids are able to act as carbon nucleophiles, i.e. enolates, in Mannich-type reactions. This reaction proceeds

  羧基 (COOH) 是有机分子中无处不在的官能团，其直接催化活化是一种有吸引力的合成方法。在此，我们描述了用 BH3·SMe2 直接催化亲核活化羧酸的第一个例子，之后酸能够在曼尼希型反应中充当碳亲核试剂，即烯醇化物。该反应使用温和的有机碱 (DBU) 进行，并表现出高水平的官能团耐受性。硼催化剂对 COOH 基团具有高度化学选择性，即使存在其他羰基部分，如酰胺、酯或酮。此外，通过使用 (R)-3,3'-I2-BINOL 取代的硼催化剂，这种催化方法可以扩展到高度对映选择性的曼尼希型反应。
• Carrier-free cellular uptake and the gene-silencing activity of the lipophilic siRNAs is strongly affected by the length of the linker between siRNA and lipophilic group
  作者：Natalya S. Petrova、Ivan V. Chernikov、Mariya I. Meschaninova、IIya S. Dovydenko、Aliya G. Venyaminova、Marina A. Zenkova、Valentin V. Vlassov、Elena L. Chernolovskaya

  DOI：10.1093/nar/gkr1002

  日期：2012.3

  The conjugation of siRNA to molecules, which can be internalized into the cell via natural transport mechanisms, can result in the enhancement of siRNA cellular uptake. Herein, the carrier-free cellular uptake of nuclease-resistant anti-MDR1 siRNA equipped with lipophilic residues (cholesterol, lithocholic acid, oleyl alcohol and litocholic acid oleylamide) attached to the 5′-end of the sense strand via oligomethylene linker of various length was investigated. A convenient combination of H-phosphonate and phosphoramidite methods was developed for the synthesis of 5′-lipophilic conjugates of siRNAs. It was found that lipophilic siRNA are able to effectively penetrate into HEK293, HepG2 and KB-8-5 cancer cells when used in a micromolar concentration range. The efficiency of the uptake is dependent upon the type of lipophilic moiety, the length of the linker between the moiety and the siRNA and cell type. Among all the conjugates tested, the cholesterol-conjugated siRNAs with linkers containing from 6 to 10 carbon atoms demonstrate the optimal uptake and gene silencing properties: the shortening of the linker reduces the efficiency of the cellular uptake of siRNA conjugates, whereas the lengthening of the linker facilitates the uptake but retards the gene silencing effect and decreases the efficiency of the silencing.

  通过与分子结合，这些分子可以通过自然运输机制进入细胞，从而增强siRNA的细胞摄取。在此，我们研究了通过不同长度的亚甲基连接子将疏水性残基（胆固醇、石胆酸、油醇和石胆酸油胺）连接到正义链的5′端，制备的耐核酸酶的抗MDR1 siRNA的无载体细胞摄取。我们开发了一种方便的H-磷酸盐和磷酰胺方法的组合，用于合成siRNA的5′-疏水性偶联物。发现当在微摩尔浓度范围内使用时，疏水性siRNA能够有效地渗透到HEK293、HepG2细胞和KB-8-5癌细胞中。摄取效率取决于疏水性部分类型、部分与siRNA之间的连接子长度以及细胞类型。在所有测试的偶联物中，含有6到10个碳原子的连接子连接的胆固醇化siRNA显示出最佳的摄取和基因沉默特性：连接子缩短会降低siRNA偶联物的细胞摄取效率，而连接子延长有助于摄取，但会延迟基因沉默效应并降低沉默效率。
• Ligand-controlled divergent dehydrogenative reactions of carboxylic acids via C–H activation
  作者：Zhen Wang、Liang Hu、Nikita Chekshin、Zhe Zhuang、Shaoqun Qian、Jennifer X. Qiao、Jin-Quan Yu

  DOI：10.1126/science.abl3939

  日期：2021.12.3

  inaccessible with existing carbonyl desaturation protocols. Product inhibition is overcome through ligand-promoted preferential activation of C(sp3)–H bonds over C(sp2)–H bonds or a tandem dehydrogenation or vinyl C–H alkynylation sequence. The dehydrogenation reaction is compatible with molecular oxygen as the terminal oxidant.

  通过亚甲基 C-H 活化将烷基链脱氢转化为烯烃仍然是一个重大挑战。我们报道了两类吡啶-吡啶酮配体，它们通过钯催化的β-亚甲基C-H活化羧酸实现不同的脱氢反应，从而直接合成α,β-不饱和羧酸或γ-亚烷基丁烯内酯。这对反应的定向性质允许在其他烯醇化官能团（例如酮）存在下对羧酸进行化学选择性脱氢，从而提供现有羰基去饱和方案无法实现的化学选择性。通过配体促进的 C(sp 3 )–H 键相对于 C(sp 2 )–H 键的优先激活或串联脱氢或乙烯基 C–H 炔基化序列来克服产物抑制。脱氢反应与分子氧作为末端氧化剂相容。
• Trifluoromethyl Benzoate: A Versatile Trifluoromethoxylation Reagent
  作者：Min Zhou、Chuanfa Ni、Yuwen Zeng、Jinbo Hu

  DOI：10.1021/jacs.8b04000

  日期：2018.6.6

  Trifluoromethyl benzoate (TFBz) is developed as a new shelf-stable trifluoromethoxylation reagent, which can be easily prepared from inexpensive starting materials using KF as the only fluorine source. The synthetic potency of TFBz is demonstrated by trifluoromethoxylation-halogenation of arynes, nucleophilic substitution of alkyl (pseudo)halides, cross-coupling with aryl stannanes, and asymmetric

  苯甲酸三氟甲酯 (TFBz) 被开发为一种新的货架稳定的三氟甲氧基化试剂，它可以很容易地从廉价的原料中制备，使用 KF 作为唯一的氟源。芳烃的三氟甲氧基化-卤化、烷基（伪）卤化物的亲核取代、与芳基锡烷的交叉偶联和烯烃的不对称双官能化证明了 TFBz 的合成效力。在冠醚络合的钾阳离子的帮助下，芳炔的前所未有的三氟甲氧基化-卤化在室温下顺利进行，这显着稳定了衍生自 TFBz 的三氟甲氧基阴离子。
• Synthesis and Anticancer Activity of Hybrid Molecules Based on Lithocholic and (5Z,9Z)-Tetradeca-5,9-dienedioic Acids Linked via Mono(di,tri,tetra)ethylene Glycol and α,ω-Diaminoalkane Units
  作者：Vladimir A. D’yakonov、Regina A. Tuktarova、Lilya U. Dzhemileva、Svetlana R. Ishmukhametova、Usein M. Dzhemilev

  DOI：10.3390/ph14020084

  日期：——

  For the first time, hybrid molecules were synthesized on the basis of lithocholic and (5Z,9Z)-1,14-tetradeca-5,9-dienedicarboxylic acids, obtained in two stages using the homo-cyclomagnesiation reaction of 2-(hepta-5,6-diene-1-yloxy)tetrahydro-2H-pyran at the key stage. The resulting hybrid molecules containing 5Z,9Z-dienoic acids are of interest as novel synthetic biologically active precursors to create modern drugs for the treatment of human oncological diseases. The synthesized hybrid molecules were found to exhibit extremely high in vitro inhibitory activity against human topoisomerase I, which is 2–4 times higher than that of camptothecin, a known topoisomerase I inhibitor. Using flow cytometry and fluorescence microscopy, it was first shown that these new molecules are efficient apoptosis inducers in HeLa, U937, Jurkat, K562, and Hek293 cell cultures. In addition, the results of investigations into the effect of the synthesized acids on mitochondria and studies of possible DNA damage in Jurkat tumor cells are also presented.

  首次，基于麻黄酸和(5Z,9Z)-1,14-十四碳-5,9-二烯二羧酸，在两个阶段使用2-(庚-5,6-二烯-1-氧基)四氢-2H-吡喃的同环合镁反应合成了杂化分子。含有5Z,9Z-二烯酸的这些杂化分子作为新型合成生物活性前体，对于开发治疗人类肿瘤疾病的现代药物具有重要意义。合成的杂化分子显示出极高的体外抑制人类拓扑异构酶I活性，比已知的拓扑异构酶I抑制剂喜树碱高2-4倍。首次利用流式细胞术和荧光显微镜观察到这些新分子在HeLa、U937、Jurkat、K562和Hek293细胞培养中是有效的凋亡诱导剂。此外，还介绍了对合成酸对线粒体的影响以及对Jurkat肿瘤细胞可能的DNA损伤研究的结果。