methyl 3α-azido-7α,12α-dihydroxy-5β-cholan-24-oate | 175340-05-3

• 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: methyl 3α-azido-7α,12α-dihydroxy-5β-cholan-24-oate
• 英文别名: methyl (4R)-4-[(3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3-azido-7,12-dihydroxy-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: 175340-05-3
• 化学式: C₂₅H₄₁N₃O₄
• 分子量: 447.618
• InChiKey: MDUASBVGFDAVFE-SRNOMOOLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  81.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 3α-azido-7α,12α-dihydroxy-5β-cholan-24-oate 在 水 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-{3-[4-(3-amino-7,12-dihydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoylamino]-7,12-dihydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl}-pentanoic acid methyl ester
  参考文献：
  名称：

  Oligomeric Cholates:  Amphiphilic Foldamers with Nanometer-Sized Hydrophilic Cavities

  摘要：

  The hydroxyl at the C-3 of cholic acid was converted to an amino group, and the resulting aminofunctionalized cholic acid was used as a monomer to prepare amide-linked oligomeric cholates. These cholate oligomers fold into helical structures with nanometer-sized hydrophilic internal cavities in solvent mixtures consisting of mostly nonpolar solvents such as carbon tetrachloride or ethyl acetate/hexane and 2-5% of a polar solvent such as methanol or DMSO. The conformations of the foldamers; were studied by UV, fluorescence, fluorescence quenching, and fluorescence resonance energy transfer. The nature of the polar/nonpolar solvents and their miscibility strongly influenced the folding reaction. Folding was cooperative, as evidenced by the sigmoidal curves in solvent denaturation experiments. The folded conformers became more stable with an increase in the chain length. The folding/unfolding equilibrium was highly sensitive toward the amount of polar solvent. One percent variation in the solvent composition could change the folding free energies by 0.5-1.4 kcal/mol.

  DOI：

  10.1021/ja056151p
• 作为产物：
  描述：

  胆酸甲酯 在 咪唑 、 sodium azide 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.58h， 生成 methyl 3α-azido-7α,12α-dihydroxy-5β-cholan-24-oate
  参考文献：
  名称：

  通过正交点击反应的荧光标记辅助合成胆汁酸-双膦酸酯共轭物：获得潜在的抗吸收性骨药物的途径

  摘要：

  据报道，合成了少量新的胆汁酸-双膦酸盐（BA-BP）偶联物作为潜在的候选药物。所披露的方法分别依赖于BA支架的头尾位置上的叠氮化物和硫醇官能团的安装以及随后通过正交点击反应（铜催化的叠氮化物-炔环加成，硫醇-烯或硫醇-炔偶联）的修饰）引入BP单元和荧光团。由于通过标准程序难以分离靶标结合物，因此该方法最终以具有轻质荧光标签的BA支架功能化，从而通过荧光固相萃取快速有效地纯化中间体和最终产物。

  DOI：

  10.1039/c7ob00774d

文献信息

• Mitsunobu reactions with methanesulfonic acid; The replacement of equatorial hydroxyl groups by azide with net retention of configuration
  作者：Anthony P. Davis、Stephan Dresen、Laurence J. Lawless

  DOI：10.1016/s0040-4039(97)00886-1

  日期：1997.6

  of equatorial cyclohexanols with Ph3P/DEAD/MsOH gives clean conversion to the axial mesylates. Subsequent reaction with NaN3 gives the equatorial azides in overall yields of 74–87%. Axial hydroxyl groups are not affected, allowing the regioselective conversion of methyl cholate into a 3α-azidodiol intermediate for steroid-based synthetic receptors.

  用Ph 3 P / DEAD / MsOH处理赤道环己醇可将其干净地转化为轴向甲磺酸酯。随后与NaN 3的反应使赤道叠氮化物的总产率为74-87％。轴向羟基不受影响，允许胆甾醇将区域选择性地转化为基于类固醇的合成受体的3α-叠氮二醇中间体。
• Improving reactivity and selectivity of aqueous-based Heck reactions by the local hydrophobicity of phosphine ligands
  作者：Gina M. Roberts、Shiyong Zhang、Yan Zhao、L. Keith Woo

  DOI：10.1016/j.tet.2015.09.010

  日期：2015.10

  affords a new ligand, 1, which is effective in palladium-catalyzed Heck cross-couplings between acrylates and aryl iodides under mild, aqueous reaction conditions. High yields, up to 99%, were achieved in water at 40 °C. In competition studies, a more hydrophobic substrate (n-Bu acrylate) was preferred over the least hydrophobic substrate (methyl acrylate), supportive of a localized hydrophobic microenvironment

  用胆酸盐部分的三芳基膦的变形，得到一个新的配体，1，这是有效的钯催化的Heck交叉偶联丙烯酸酯和芳基碘之间温和，含水反应条件下进行。在40°C的水中可实现高达99％的高收率。在竞争研究中，更疏水基质（Ñ -Bu丙烯酸酯）中的溶液，优选在至少疏水性基材（丙烯酸甲酯），支持靠近催化中心的局部微环境的疏水性的。当本地疏水性是使用标准的水溶性膦或在有机溶剂中消除了疏水性衬底的增强的反应性和选择性消失。
• Two-channel dansyl/tryptophan emitters with a cholic acid bridge as reporters for local hydrophobicity within supramolecular systems based on bile salts
  作者：M. Gomez-Mendoza、M. Luisa Marin、Miguel A. Miranda

  DOI：10.1039/c4ob01394h

  日期：——

  Simultaneous emission from the Trp and Dns fluorophores of linked dyads in biomimetic media is quenched by iodide anions with rate constants that depend on the local hydrophobicity.

  在仿生介质中，由于碘离子的存在，与Trp和Dns荧光团结合的偶联双聚体同时发射的发射被抑制，其速率常数取决于局部疏水性。
• Steroidal guanidines as enantioselective receptors for N-acyl α-amino acids. Part 1. 3α-Guanylated carbamates derived from cholic acid
  作者：Laurence J. Lawless、Adrian G. Blackburn、Alan J. Ayling、M. Nieves Pérez-Payán、Anthony P. Davis

  DOI：10.1039/b009215k

  日期：——

  other functional groups, were synthesized from cholic acid 1. These cations were shown to extract chiral carboxylate anions from aqueous buffer into chloroform with significant enantioselectivities. The most successful receptors bore two carbamate substituents and achieved, in the best cases, ratios (L:D) of 7–10:1 for a series of five N-acetyl α-amino acids.

  胆碱酸1合成了带有胍基，氨基甲酸酯和（在某些情况下）其他官能团的5-11受体。这些阳离子显示出从水缓冲液中将手性羧酸根阴离子提取到氯仿中的对映体选择性很高。最成功的受体带有两个氨基甲酸酯取代基，在最佳情况下，一系列五个N-乙酰基α-氨基酸的比率（L：D）达到7–10：1 。
• Synthesis and in vitro cytotoxicity of deoxyadenosine–bile acid conjugates linked with 1,2,3-triazole
  作者：Daniela Perrone、Olga Bortolini、Marco Fogagnolo、Elena Marchesi、Lara Mari、Chiara Massarenti、Maria Luisa Navacchia、Fabio Sforza、Katia Varani、Massimo Luigi Capobianco

  DOI：10.1039/c3nj00513e

  日期：——

  report herein the synthesis and biological evaluation of novel deoxynucleoside–bile acid conjugates linked through a 1,2,3-triazole ring. The conjugates were synthesized via Cu(I) mediated 1,3-dipolar cycloaddition reaction (‘click’ chemistry) of 3-azidobile acid derivatives and terminal alkyne moieties linked to the C-8 position of deoxyadenosine. All novel molecules were evaluated in vitro for their

  我们在这里报告了通过1,2,3-三唑环连接的新型脱氧核苷-胆汁酸缀合物的合成和生物学评估。通过Cu（I）介导的3-叠氮胆酸衍生物和与脱氧腺苷的C-8位相连的末端炔基部分的1，3-偶极环加成反应（“点击”化学）合成了缀合物。在体外评估了所有新分子对四种人类细胞系（即白血病T Jurkat和K562；结肠癌HCT116；和卵巢癌A2780）的抗增殖活性以及对人成纤维细胞的细胞毒性。几种缀合物显示出对人白血病T细胞的强抗增殖活性。观察到最佳的细胞毒性两种白血病细胞系上的HdA-CDC的IC 50最高为8.51μM。还确定了几种缀合物的凋亡活性。