diketene acetal (3,9-bis(ethylidene)-2,4,8,10-tetraoxaspiro<5,5>undecane) | 65967-52-4

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二恶烷
• 英文名称: diketene acetal (3,9-bis(ethylidene)-2,4,8,10-tetraoxaspiro<5,5>undecane)
• 英文别名: 3,9-diethylidene-2,4,8,10-tetraoxaspiro-[5.5]undecane；3,9-diethylidene-2,4,8,10-tetraoxaspiro[5.5]undecane；DETOSU；3,9-bis-(ethylidene)-2,4,8,10-tetraoxaspiro [5,5] undecane；3, 9-diethylidene-2,4, 8,10-tetraoxaspiro[5.5]undecane；3,9-di(ethylidene)-2,4,8,10-tetraoxaspiro[5,5]undecane
• CAS: 65967-52-4
• 化学式: C₁₁H₁₆O₄
• 分子量: 212.246
• InChiKey: ZNCFMBOWBMPEAC-UIYSNZQUSA-N

物化性质

• 沸点：
  357.1±42.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.79
• 重原子数：
  15.0
• 可旋转键数：
  0.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  36.92
• 氢给体数：
  0.0
• 氢受体数：
  4.0

安全信息

• 包装等级：
  III
• 危险类别：
  9
• 危险性防范说明：
  P501,P273,P260,P270,P264,P280,P391,P314,P337+P313,P305+P351+P338,P301+P312+P330
• 危险品运输编号：
  3077
• 危险性描述：
  H302,H319,H372,H410
• 储存条件：
  -20°C，惰性气体

反应信息

• 作为反应物：
  描述：

  diketene acetal (3,9-bis(ethylidene)-2,4,8,10-tetraoxaspiro<5,5>undecane) 在 对甲苯磺酸 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 1-(3-ethyl-3-dodecyloxy-9-ethyl-2,4,8,10-tetraoxaspiro[5.5]undecan-9-yloxy)-2-oleylglycero-3-phosphatidylcholine
  参考文献：
  名称：

  Acid-Triggered Transformation of Diortho Ester Phosphocholine Liposome

  摘要：

  The use of pH-sensitive liposomes for acid-triggered site-specific drug delivery is one of the more promising approaches to improve the therapeutic index of drugs. Here, we report the synthesis, assembly, and hydrolysis of the first ortho ester phosphocholine (OEPC). The acid hydrolysis of OEPC liposomes consists of a lag phase and a burst phase. The lag time is pH-dependent-the lower the pH, the shorter the time. Upon acid hydrolysis, the OEPC liposomes were transformed into leaky metastable vesicles that rapidly collapsed in the presence of albumin. OEPC, when formulated with cationic lipid, significantly enhanced the transfection efficiency compared with that of the pH-insensitive formulation.

  DOI：

  10.1021/ja057024w
• 作为产物：
  描述：

  3,9-二乙烯基-2,4,8,10-四氧杂螺[5.5]十一烷 在 iron pentacarbonyl 作用下， 以 正戊烷 为溶剂， 反应 2.67h， 以82%的产率得到diketene acetal (3,9-bis(ethylidene)-2,4,8,10-tetraoxaspiro<5,5>undecane)
  参考文献：
  名称：

  [EN] METHOD OF PREPARING DI(KETENE ACETALS)
  [FR] PROCEDE DE PREPARATION DE DI(CETENE ACETALS)

  摘要：

  Di（酮烯缩醛）是通过光异构化相应的双（乙烯醇醚）制备的。

  公开号：

  WO2004046074A1

文献信息

• Base-stabilized polyorthoester formulations
  申请人：Shah T. Devang

  公开号：US20070264338A1

  公开（公告）日：2007-11-15

  A stabilized semi-solid delivery vehicle contains a polyorthoester and an excipient, and a pharmaceutical composition contains an active agent, optionally a stabilizing agent, and the delivery vehicle. The pharmaceutical composition may be a topical, syringable, or injectable formulation; and is suitable for local delivery of the active agent. Methods of treatment are also disclosed.

  一种稳定的半固态给药载体包含聚正交酯和辅料，以及一种药物组合物包含活性药剂，可选地包含稳定剂和给药载体。该药物组合物可以是局部、可注射或可注射的配方；适用于活性药剂的局部给药。还公开了治疗方法。
• PEG-POE, PEG-POE-PEG, and POE-PEG-POE block copolymers
  申请人：——

  公开号：US20030152630A1

  公开（公告）日：2003-08-14

  PEG-POE, PEG-POE-PEG, and POE-PEG-POE block copolymers have both hydrophilic and hydrophobic blocks. They form micelles in aqueous solution, making them suitable for encapsulation or solubilization of hydrophobic or water-insoluble materials; and they also form bioerodible matrices for the sustained release of active agents, especially when the POE block(s) contain at least one unit containing an &agr;-hydroxy acid.

  PEG-POE，PEG-POE-PEG和POE-PEG-POE嵌段共聚物具有亲水和疏水区块。它们在水溶液中形成胶束，适用于包封或溶解疏水或不溶于水的材料；它们还形成可生物降解的基质，用于持续释放活性剂，特别是当POE区块中至少含有一个含有α-羟基酸的单元时。
• Chimeric immunomodulatory compounds and methods of using the same - III
  申请人：——

  公开号：US20030225016A1

  公开（公告）日：2003-12-04

  The invention provides immunomodulatory compounds and methods for immunomodulation of individuals using the immunomodulatory compounds.

  这项发明提供了免疫调节化合物以及利用这些免疫调节化合物对个体进行免疫调节的方法。
• Dendrimeric Alkylated Polyethylenimine Nano-carriers with Acid-Cleavable Outer Cationic Shells Mediate Improved Transfection Efficiency Without Increasing Toxicity
  作者：Terry W. J. Steele、Wayne Thomas Shier

  DOI：10.1007/s11095-010-0058-1

  日期：2010.4

  Improved polycation-based non-viral DNA vectors were sought by preparing dendrimers with polyethylenimine cores surrounded by various shells incorporating structural features intended to facilitate steps in transfection mechanisms. Dendrimeric vectors were designed with (a) an outer oligocation shell, intended to facilitate DNA release inside cells, (b) a hydrophobic C-16 alkyl shell, and (c) a polycationic core, the latter two intended to combine lipid-depletion and osmotic burst endosome escape mechanisms, respectively, and were (d) attached through an a acid-cleavable linker reported to hydrolyze at endosomal pH values. Vectors and DNA complexes were characterized by dynamic and static light scattering. Flow cytometry was used to quantitate transfection activity and cytotoxicity in CHO–K1 cells. About 5-fold increased transfection activity was obtained for a vector constructed with an outer shell of oligocations attached through acid-cleavable linkers, relative to a control dendrimer with an acid-stable linker. The most effective oligocation component of outer shells tested was spermine. Neither modification was associated with increased cytotoxicity. This vector design did not permit an evaluation of the benefit of combining endosome release mechanisms. Using acid-cleavable linkers to attach an outer shell of short, highly-charged oligocations to a PEI-based dendrimeric vector substantially increased transfection efficiency without increasing cytotoxicity.

  通过制备具有聚乙烯亚胺核的树枝状聚合物，并在其周围包覆各种具有结构特征的外壳，以促进转染机制中的各个步骤，从而寻求改进的基于多阳离子的非病毒 DNA 载体。设计的树枝状载体(a)具有寡定位外壳，旨在促进 DNA 在细胞内的释放；(b)具有疏水的 C-16 烷基外壳；(c)具有多阳离子核心，后两者分别旨在结合脂质耗竭和渗透猝灭内体逃逸机制；(d)通过据报道在内体 pH 值下可水解的酸可分解连接体连接。通过动态和静态光散射对载体和 DNA 复合物进行了表征。流式细胞仪用于量化 CHO-K1 细胞中的转染活性和细胞毒性。与使用酸稳定连接体的对照树枝状聚合物相比，通过酸可分解连接体连接了寡定位外壳的载体的转染活性提高了约 5 倍。经测试，外壳中最有效的寡定位成分是精胺。这两种修饰都不会增加细胞毒性。这种载体设计无法评估结合内质体释放机制的益处。使用酸可分解连接体在基于 PEI 的树枝状聚合物载体上连接一个短的、高电荷的寡配位体外壳，可在不增加细胞毒性的情况下大幅提高转染效率。
• Polymers containing poly(ester amides) and agents for use with medical articles and methods of fabricating the same
  申请人：Pacetti D. Stephen

  公开号：US20050265960A1

  公开（公告）日：2005-12-01

  Polymers containing poly(ester amides) and agents for use with medical articles and methods of fabricating the same are disclosed. The medical article generally comprises an implantable substrate having a coating, and the coating contains a polymer comprising a polymeric product of a reaction comprising a polyol, a polycarboxylic acid, an amino acid and an agent.

  本发明揭示了含有聚（酯酰胺）的聚合物以及用于医疗器械的药剂和制备方法。医疗器械通常包括具有涂层的可植入基质，涂层含有聚合物，该聚合物是由聚醇、聚羧酸、氨基酸和药剂反应生成的聚合产物组成。