α-benzyl carboxylate-ε-caprolactone | 918159-71-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: α-benzyl carboxylate-ε-caprolactone
• 英文别名: Benzyl 2-oxooxepane-3-carboxylate
• CAS: 918159-71-4
• 化学式: C₁₄H₁₆O₄
• 分子量: 248.279
• InChiKey: VUUHMTRRQHHIQH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-己内酯 、 氯甲酸苄酯 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以45%的产率得到α-benzyl carboxylate-ε-caprolactone
  参考文献：
  名称：

  用于钕和铈络合的功能性羧酸基聚(εCL-st-αCOOHεCL)-b-PEG-b-聚(εCL-st-αCOOHεCL)共聚物的合成与评价

  摘要：

  最初的羧酸基共聚物已被开发用于锕系元素的络合。为此，α-羧酸苄酯-ε-己内酯 (BzCL) 和 ε-己内酯 (εCL) 的开环共聚已在聚乙二醇 (PEG) 作为大分子引发剂和辛酸锡 (II) 的情况下进行，作为催化剂，得到聚(εCL- st -αBzεCL)- b -PEG- b -poly(εCL- st -αBzεCL) (PB) 共聚物。以三种不同的 εCL/BzCL 比率为目标（90/10、75/25 和 50/50），分别导致 PB 10%、PB 25%和 PB 50%。然后，对制备的共聚物进行氢化，使苄酯脱保护为羧酸基团，得到聚（εCL-ST -αCOOHεCL） - b -PEG- b -聚（εCL- ST -αCOOHεCL）共聚物（PA 10％，PA 25％和PA 50％ ）。所有材料均通过1 H NMR、13 C NMR 和尺寸排阻色谱法进行了充分表征。发现实验比率与理论比率接近，等于

  DOI：

  10.1016/j.reactfunctpolym.2021.105157

文献信息

• Multifunctional Polymeric Micelles for Enhanced Intracellular Delivery of Doxorubicin to Metastatic Cancer Cells
  作者：Xiao-Bing Xiong、Abdullah Mahmud、Hasan Uludağ、Afsaneh Lavasanifar

  DOI：10.1007/s11095-008-9673-5

  日期：2008.11

  To develop multifunctional RGD-decorated poly(ethylene oxide)-b-poly(ester) based micelles and assess their pH-triggered core degradation and targeted drug release in tumor cells that overexpress RGD receptors. Novel poly(ethylene oxide)-b-poly(ε-caprolactone) (PEO-b-PCL) based copolymers modified with RGD ligands on PEO and pendent functional groups on PCL, i.e., GRGDS-PEO-b-poly(α-benzylcarboxylate-ε-caprolactone) (GRGDS-PEO-b-PBCL) and GRGDS-PEO-b-poly(α-carboxyl-ε-caprolactone) (GRGDS-PEO-b-PCCL), were synthesized. Chemical conjugation of doxorubicin (DOX) to PCCL core produced GRGDS-PEO-b-P(CL-DOX) micellar conjugates, while GRGDS-PEO-b-PBCL were used to physically encapsulate DOX. For both systems, micellar core degradation, drug release, intracellular drug uptake/disposition, and cytotoxicity against B16F10 metastatic cells were investigated. The PBCL and P(CL-DOX) cores were found resistant to degradation in pH 7.2, but showed 10% and 40% loss in core molecular weight in pH 5.0 within 144 h, respectively. Preferential release of DOX and DOX derivatives from PBCL and P(CL-DOX) cores was noted in pH 5.0, respectively. The GRGDS-modified micelles showed enhanced cellular internalization through endocytosis, increased intracellular DOX release, nuclear localization, and improved cytotoxicity against metastatic B16F10 cells compared to their unmodified counterparts. The results clearly suggest a promise for the development of multifunctional polymeric micelles with RGD ligand decorated shell and endosomal pH-triggered degradable core for selective DOX delivery to metastatic cancer cells.

  开发多功能的RGD修饰聚乙烯氧化物-聚酯基础的胶束，并评估其在过表达RGD受体的肿瘤细胞中pH触发的核心降解和靶向药物释放。合成了新型聚乙烯氧化物-聚(ε-己内酯)(PEO-b-PCL)基础的共聚물，这些共聚物在PEO上修饰了RGD配体，并在PCL上具备侧链功能团，即GRGDS-PEO-b-聚(α-苄基羧酸-ε-己内酯)(GRGDS-PEO-b-PBCL)和GRGDS-PEO-b-聚(α-羧酸-ε-己内酯)(GRGDS-PEO-b-PCCL)。通过化学结合的方法将多柔比星(DOX)连接到PCCL核心，制备了GRGDS-PEO-b-P(CL-DOX)胶束复合物，而GRGDS-PEO-b-PBCL则用于物理包封DOX。对这两种体系进行了胶束核心降解、药物释放、细胞内药物摄取/分布以及对B16F10转移细胞的细胞毒性研究。PBCL和P(CL-DOX)核心在pH 7.2下对降解具有抗性，但在pH 5.0下144小时内核心分子量分别减少10%和40%。在pH 5.0下，观察到DOX及其衍生物从PBCL和P(CL-DOX)核心的优先释放。与未修饰的胶束相比，GRGDS修饰的胶束表现出通过内吞作用增强的细胞内吞、增加的细胞内DOX释放、细胞核定位以及对转移性B16F10细胞的细胞毒性改善。结果清楚表明，开发具有RGD配体修饰外壳和内源性pH触发降解核心的多功能聚合物胶束在选择性DOX递送到转移性癌细胞方面具有良好前景。
• Functionalized caprolactone monomers useful for making poly(ethylene oxide)-block-poly(ester) block copolymers
  申请人：The Governors of the University of Alberta

  公开号：EP2730604A2

  公开（公告）日：2014-05-14

  A compound of formula II: wherein L1 is a linker group selected from the group consisting of a single bond, -C(O)-O-, - C(O)- and -C(O)NR2; R1 is selected from the group consisting of H, OH, C1-20 alkyl, C3-20 cycloalkyl and aryl, said latter three groups may be optionally substituted and in which one or more of the carbons of the alkyl, cycloalkyl or aryl groups may optionally be replaced with O, S, N, NR2 or N(R2)2; R2 is H or C1-6 alkyl; and v is an integer from 1 to 4; wherein aryl is mono- or bi-cyclic aromatic radical containing from 6 to 14 carbon atoms having a single ring or multiple condensed rings; and wherein the optional substituents are selected from the group consisting of halo, OH, OC1-6 alkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkenyloxy, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)(C1-6 alkyl), CN, NO2, C(O)C1-6 alkyl, C(O)OC1-6 alkyl, SO2C1-6 alkyl, SO2NH2, SO2NHC1-6 alkyl, phenyl and C1-6 alkylenephenyl.

  式 II 的化合物： 其中 L1 是一个连接基团，选自由单键、-C(O)-O-、-C(O)- 和 -C(O)NR2 组成的组； R1 选自 H、OH、C1-20 烷基、C3-20 环烷基和芳基组成的组，后三个基团可被任选取代，其中 烷基、环烷基或芳基的一个或多个碳可任选被 O、S、N、NR2 或 N(R2)2 取代； R2 是 H 或 C1-6 烷基；以及 v 是 1 到 4 的整数； 其中芳基是含有 6 至 14 个碳原子的单环或双环芳香基，具有单环或多个缩合环；以及 其中任选取代基选自卤、OH、OC1-6 烷基、C1-6 烷基、C2-6 烯基、C2-6 烯氧基、NH2、NH(C1-6 烷基)、N(C1-6 烷基)(C1-6 烷基)、CN、NO2、C(O)C1-6 烷基、C(O)OC1-6 烷基、SO2C1-6 烷基、SO2NH2、SO2NHC1-6 烷基、苯基和 C1-6 烯基苯基组成的组。
• NOVEL POLY(ETHYLENE OXIDE)-BLOCK-POLY(ESTER) BLOCK COPOLYMERS
  申请人：The Governors of the University of Alberta

  公开号：EP1994081B1

  公开（公告）日：2014-05-21
• NOVEL LIGAND GUIDED BLOCK COPOLYMERS FOR TARGETED DRUG DELIVERY
  申请人：Lavasanifar Afsaneh

  公开号：US20100137206A1

  公开（公告）日：2010-06-03

  This application relates to micelle-forming poly(ethylene oxide)-block-poly(ester) block copolymers having reactive groups on both the poly(ethylene oxide) block and the poly(ester) block therein. The biodegradability of these copolymers and their biocompatibilities with a large number of bioactive agents make them suitable as carriers for various bioactive agents. The bioactive agent, such as DNA, RNA, oligonucleotide, protein, peptide, drug and the like, can be coupled to the reactive groups on the polyester block of the copolymer. A variety of targeting moieties can be coupled to the reactive group on the poly(ethylene oxide) block for targeting the bioactive agent to a particular tissue. The application also relates to a composition and method of use thereof for delivering bioactive agents.
• US8309515B2
  申请人：——

  公开号：US8309515B2

  公开（公告）日：2012-11-13