per-O-propionyl-β-cyclodextrin

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: per-O-propionyl-β-cyclodextrin
• 英文别名: tripropanoyl β-cyclodextrin；tripropanoyl β-CD；TP-β-CD；[(1R,3R,5R,6R,8R,10R,11R,13R,15R,16R,18R,20R,21R,23R,25R,26R,28R,30R,31R,33R,35R,36S,37R,38S,39R,40S,41R,42S,43R,44S,45R,46S,47R,48S,49R)-36,37,38,39,40,41,42,43,44,45,46,47,48,49-tetradeca(propanoyloxy)-10,15,20,25,30,35-hexakis(propanoyloxymethyl)-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontan-5-yl]methyl propanoate
• 化学式: C₁₀₅H₁₅₄O₅₆
• 分子量: 2312.34
• InChiKey: ULWMUZLYDTWZAR-KRKLWNNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  161
• 可旋转键数：
  70
• 环数：
  21.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  682
• 氢给体数：
  0
• 氢受体数：
  56

反应信息

• 作为产物：
  描述：

  丙酸酐 、 β-环糊精 在 吡啶 作用下， 反应 24.0h， 以62%的产率得到per-O-propionyl-β-cyclodextrin
  参考文献：
  名称：

  Characterization of Peracylated .BETA.-Cyclodextrins with Different Chain Lengths as a Novel Sustained Release Carrier for Water-Soluble Drugs.

  摘要：

  一种新的醇酰化β-环糊精（β-CyD）系列，采用不同的烷基链（醋酸-月桂酰基）在高纯度下制备，通过在吡啶中使用酸酐对β-CyD的所有羟基进行酰化，并评估了其在溶解度、水解、释放和相互作用能力方面的物理化学性质。醇酰化β-CyDs在水中的溶解度随着烷基链的延长而降低，而在乙醇/水中的溶解度则随着乙醇浓度的增加而增加，但在较高乙醇浓度下则趋于降低。通过分析峰值溶解现象，采用改进的希尔德布兰德方程确定了醇酰化β-CyDs的溶解度参数。醇酰化β-CyDs的碱性水解速率随着烷基链的延长而降低，且约为相应脂肪酸乙酯的4倍。通过差示扫描量热法（DSC）研究了铂丁酰-β-CyD（TB-β-CyD）与一种水溶性药物莫沙吡啶在固态下的相互作用。DSC曲线的分析表明，莫沙吡啶与TB-β-CyD形成一种2:1（药物:TB-β-CyD）摩尔比的二元固体分散体。药物释放速率因与醇酰化β-CyDs的结合而显著减缓，且减缓程度按宿主分子的疏水性递增排列。

  DOI：

  10.1248/cpb.43.130

文献信息

• Characterization of Peracylated .BETA.-Cyclodextrins with Different Chain Lengths as a Novel Sustained Release Carrier for Water-Soluble Drugs.
  作者：Fumitoshi HIRAYAMA、Masayuki YAMANAKA、Takashi HORIKAWA、Kaneto UEKAMA

  DOI：10.1248/cpb.43.130

  日期：——

  A new series of peracylated β-cyclodextrins (β-CyDs) with different alkyl chains (acetyl-lauroyl) was prepared in high purity by acylating all hydroxyl groups of β-CyD using acid anhydrides in pyridine, and their physicochemical properties of solubility, hydrolsis and release and interaction capacity were evaluated. The solublity of peracylated β-CyDs in water decreased with lengthening alkyl chain, whereas that in ethanol/water increased with increase in ethanol concentration, but tended to decrease at higher ethanol concentration. The solubility parameter of peracylated β-CyDs was determined by analyzing the peak-solubility phenomenon by a modified Hildebrand equation. The alkaline hydrolysis rate of peracylated β-CyDs decreased with lengthening alkyl chain, and was about 4-fold faster than that of the corresponding fatty acid ethyl esters. The interaction of perbutanoyl-β-CyD (TB-β-CyD) with a water-soluble drug, molsidomine, in the solid state was investigated by differential scanning calorimetry (DSC). The analysis of DSC curves suggested that molsidomine and TB-β-CyD form a binary solid dispersion with a 2 : 1 (drug : TB-β-CyD) molar ratio. The rate of drug release was markedly retarded by the combination with peracylated β-CyDs in the increasing order of the hydrophobicity of host molecules.

  一种新的醇酰化β-环糊精（β-CyD）系列，采用不同的烷基链（醋酸-月桂酰基）在高纯度下制备，通过在吡啶中使用酸酐对β-CyD的所有羟基进行酰化，并评估了其在溶解度、水解、释放和相互作用能力方面的物理化学性质。醇酰化β-CyDs在水中的溶解度随着烷基链的延长而降低，而在乙醇/水中的溶解度则随着乙醇浓度的增加而增加，但在较高乙醇浓度下则趋于降低。通过分析峰值溶解现象，采用改进的希尔德布兰德方程确定了醇酰化β-CyDs的溶解度参数。醇酰化β-CyDs的碱性水解速率随着烷基链的延长而降低，且约为相应脂肪酸乙酯的4倍。通过差示扫描量热法（DSC）研究了铂丁酰-β-CyD（TB-β-CyD）与一种水溶性药物莫沙吡啶在固态下的相互作用。DSC曲线的分析表明，莫沙吡啶与TB-β-CyD形成一种2:1（药物:TB-β-CyD）摩尔比的二元固体分散体。药物释放速率因与醇酰化β-CyDs的结合而显著减缓，且减缓程度按宿主分子的疏水性递增排列。
• A Simple and Convenient Per-O-acylation of Cyclodextrins Catalyzed by Molecular Iodine
  作者：Tsugio Kitamura、Yasuhiro Ide、Yuji Hori、Soichi Kobayashi、Md. Hossain

  DOI：10.1055/s-0030-1258163

  日期：2010.9

  Per-O-acylated cyclodextrins with different alkyl chains were prepared in good to high yields by iodine-catalyzed acylation of all hydroxy groups of cyclodextrins with carboxylic anhydrides under solvent-free conditions.

  在无溶剂条件下，通过用羧酸酐对环糊精的所有羟基进行碘催化酰化，以良好至高产率制备了具有不同烷基链的全O-酰化环糊精。
• Emulsion Preparation Using .BETA.-Cyclodextrin and Its Derivatives Acting as an Emulsifier
  作者：Motoki Inoue、Kaname Hashizaki、Hiroyuki Taguchi、Yoshihiro Saito

  DOI：10.1248/cpb.56.1335

  日期：——

  The preparation and formation mechanism of n-hexadecane/water emulsions using natural β-cyclodextrin (β-CD) and chemically modified β-CDs (triacylated β-cyclodextrins) as an emulsifier were investigated. The stable water/oil (W/O) emulsion was formed using tripropanoyl-β-CD (TP-β-CD). From observation using the contact angle (θow) of precipitates derived from CD, it was clarified that oil/water (O/W) emulsion at θow<90° and (W/O) emulsion at θow>90° are formed when the composition of each oil and water was mixed with natural β-CD or triacylated β-CDs.

  研究了以天然β-环糊精（β-CD）和化学修饰β-CD（三酰化β-环糊精）为乳化剂的正十六烷/水乳液的制备和形成机理。使用三丙酰-β-CD（TP-β-CD）形成了稳定的水/油（W/O）乳液。通过使用 CD 衍生沉淀物的接触角（θow）进行观察，可以明确当每种油和水的成分与天然 β-CD 或三酰化 β-CD 混合时，会形成θow<90°的油/水（O/W）乳液和θow>90°的（W/O）乳液。
• Peracylated β-Cyclodextrins as Novel Sustained-release Carriers for a Water-soluble Drug, Molsidomine
  作者：Kaneto Uekama、Takashi Horikawa、Masayuki Yamanaka、Fumitoshi Hirayama

  DOI：10.1111/j.2042-7158.1994.tb03889.x

  日期：2011.4.12

  Peracylated β-cyclodextrins with different alkyl chains (acetyl-octanoyl) were prepared by acylating all hydroxyl groups of β-cyclodextrin (β-CyD), and their physical properties were evaluated. These hydrophobic β-CyDs decreased the release rate of molsidomine, a peripheral vasodilator, in proportion to the lengthening of alkyl chain and suppressed a peak plasma level of molsidomine following oral administration of peracylated β-CyD complexes to dogs. Among the peracylated β-CyDs tested, perbutanoyl-β-CyD maintained sufficient plasma drug levels for a long period of time, while other peracylated β-CyDs having shorter or longer chains were inappropriate to control the in-vivo release behaviour of molsidomine. The prominent retarding effect of perbutanoyl-β-CyD was ascribable to the appropriate mucoadhesive property and hydrophobicity, compared with other peracylated β-CyDs. The present results suggest that perbutanoyl-β-CyD is particularly useful in modifying the release rate of water-soluble drugs as a novel slow-release carrier.

  通过酰化β-环糊精（β-CyD）的所有羟基，制备了具有不同烷基链（乙酰-辛酰）的过酰化β-环糊精，并评估了它们的物理性质。这些疏水性β-CyD随着烷基链的延长而降低了周围血管扩张剂莫西多明的释放速率，并通过口服给犬类的过酰化β-CyD复合物抑制了莫西多明的峰值血浆水平。在测试的过酰化β-CyD中，过丁酰-β-CyD维持了足够长时间的血药平衡，而其他烷基链较短或较长的过酰化β-CyD则不适合控制莫西多明的体内释放行为。与其他过酰化β-CyD相比，过丁酰-β-CyD的显著减缓效果可归因于其适当的黏附性和疏水性。本研究结果表明，过丁酰-β-CyD作为一种新型缓释载体，特别适用于调节水溶性药物的释放速率。