1,1-di-tert-butyl 3-(2-(methacryloyloxy)ethyl) butane-1,1,3-tricarboxylate | 1337993-06-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 1,1-di-tert-butyl 3-(2-(methacryloyloxy)ethyl) butane-1,1,3-tricarboxylate
• 英文别名: 1-O,1-O-ditert-butyl 3-O-[2-(2-methylprop-2-enoyloxy)ethyl] butane-1,1,3-tricarboxylate
• CAS: 1337993-06-2
• 化学式: C₂₁H₃₄O₈
• 分子量: 414.496
• InChiKey: HGJCCQZXZRVOOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  105
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  乙二醇二甲基丙烯酸酯 、 丙二酸二叔丁酯 在 18-冠醚-6 、 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 49.0h， 以56%的产率得到1,1-di-tert-butyl 3-(2-(methacryloyloxy)ethyl) butane-1,1,3-tricarboxylate
  参考文献：
  名称：

  Block Copolymer Micelles with Pendant Bifunctional Chelator for Platinum Drugs: Effect of Spacer Length on the Viability of Tumor Cells

  摘要：

  Three monomers with 1,3-dicarboxylate functional groups but varying spacer lengths were synthesized via carbon Michael addition using malonate esters and ethylene-(MAETC), butylene- (MABTC), and hexylene (MAHTC) glycol dimethacrylate, respectively. Poly[oligo-(ethylene glycol) methylether methacrylate] (POEGMEMA) was prepared in the presence of a RAFT (reversible addition-fragmentation chain transfer) agent, followed by chain extension with the prepared monomers to generate three different block copolymers (BP-E80, BP-B82, and BP-H79) with similar numbers of repeating units, but various spacer lengths as distinguishing features. Conjugation with platinum drugs created macromolecular platinum drugs resembling carboplatin. The amphiphilic natures of these Pt-containing block copolymers led to the formation micelles in solution. The rate of drug release of all micelles was similar, but a noticeable difference was the increasing stability of the micelle against dissociation with increasing spacer length. The platinum conjugated polymer showed high activity against A549, OVCAR3, and SKOV3 cancer cell lines exceeding the activity of carboplatin., but only the micelle based on the longest spacer had IC50 values as low as cisplatin. Cellular uptake studies identified a better micelle uptake with increasing micelle stability as a possible reason for lower IC50 values. The clonogenic assay revealed that micelles loaded with platinum drugs, in contrast to low molecular weight carboplatin, have not only better activity within the frame of a 72 h cell viability study, but also display a longer lasting effect by preventing the colony formation A549 for more than 10 days.

  DOI：

  10.1021/bm2017299

文献信息

• Polymeric Micelles with Pendant Dicarboxylato Chelating Ligands Prepared via a Michael Addition for <i>cis</i>-Platinum Drug Delivery
  作者：Vien T. Huynh、Paul de Souza、Martina H. Stenzel

  DOI：10.1021/ma2016503

  日期：2011.10.25

  A new monomer with a neighboring carboxylate functional group was prepared via carbon Michael addition between ethylene glycol dimethacrylate and malonate. The monomer, 1,1-di-tert-butyl 3-(2-(methacryloyloxy)ethyl) butane-1,1,3-tricarboxylate (MAETC), was polymerized in a controlled manner using RAFT polymerization. After deprotection and the conjugation of platinum drugs, a macromolecular Pt complex was created, which was found to be insoluble in water. Pt-195 NMR revealed that the desired complex has been formed next to a minor fraction of other Pt complexes. Block copolymers were prepared using poly[oligo (ethylene glycol) methyl ether methacrylate] (POEGMEMA) as macroRAFT agent for chain extension with the synthesized monomer to yield three different block copolymers with varying PMAETC block lengths. Subsequent conjugation to platinum resulted in amphiphilic block copolymers, which can ultimately generate micelles. The length of the core block had significant contribution to the micelle sizes with the micelle size increasing with an increase of the hydrophobic block length. The polymers prior to platinum conjugation were found to be nontoxic when in contact with A549, a lung cancer cell line. After conjugation with the platinum drug, the micelle with the shortest PMAETC block length was found to have the highest toxicity, which may be due to the fastest cisplatin release when compared to the longer PMAETC block lengths.