(4R)-4-[(4-methoxyphenoxy)methyl]-2,2-dimethyl-1,3-dioxolane | 1190193-88-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (4R)-4-[(4-methoxyphenoxy)methyl]-2,2-dimethyl-1,3-dioxolane
• CAS: 1190193-88-4
• 化学式: C₁₃H₁₈O₄
• 分子量: 238.284
• InChiKey: AIEFXBWJQHZGJZ-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  36.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4R)-4-[(4-methoxyphenoxy)methyl]-2,2-dimethyl-1,3-dioxolane 在 四丁基碘化铵 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 49.0h， 生成 (2R)-1-(4-methoxyphenoxy)-3-[(4-methoxyphenyl)-diphenylmethoxy]propan-2-ol
  参考文献：
  名称：

  Structure–Activity Relationships of Lysophosphatidylserine Analogs as Agonists of G-Protein-Coupled Receptors GPR34, P2Y10, and GPR174

  摘要：

  Lysophosphatidylserine (LysoPS) is an endogenous lipid mediator generated by hydrolysis of membrane phospholipid phosphatidylserine. Recent ligand screening of orphan G-protein-coupled receptors (GPCRs) identified two LysoPS specific human GPCRs, namely, P2Y10 (LPS2) and GPR174 (LPS3), which, together with previously reported GPR34 (LPS1), comprise a LysoPS receptor family. Herein, we examined the structure-attivity relationships of a series of synthetic LysoPS analogues toward these recently deorphanized LysoPS,receptors, based on the idea that LysoPS can be regarded as consisting of distinct modules (fatty acid, glycerol, and L-Serine) connected by phosphodiester and ester linkages. Starting from the endogenous ligand (1-oleoyl-LysolPS, 1), we optimized the structure of each module and the ester linkage. Accordingly, we identified some structural requirements of each module for potency and for receptor subtype selectivity. Further assembly of individually structure-optimized modules yielded a series of potent and LysoPS receptor subtype-selective agonists, particularly for P2Y10 and GPR174.

  DOI：

  10.1021/jm5020082
• 作为产物：
  描述：

  4-甲氧基苯酚 、 (R)-(-)-甘油醇缩丙酮 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 甲苯 为溶剂， 反应 3.0h， 以94%的产率得到(4R)-4-[(4-methoxyphenoxy)methyl]-2,2-dimethyl-1,3-dioxolane
  参考文献：
  名称：

  Amphiphilic Phospholipid-Based Riboflavin Derivatives for Tumor Targeting Nanomedicines

  摘要：

  核黄素（RF）是细胞代谢所必需的维生素。最新研究表明，RF通过RF转运蛋白进行内化，而前列腺癌和乳腺癌细胞以及血管生成内皮细胞中转运蛋白的表达量非常高。在此，我们介绍了一种优化的合成方案，利用亚磷酰胺化学方法制备定制的基于磷脂的RF衍生物。制备的RF两亲化合物——RfdiC14——可以插入脂质体配方中，用于靶向药物递送。所得脂质体的流体动力学尺寸为115±5 nm，尺寸分布窄（PDI 0.06），Zeta电位为-52±3 mV。体外摄取研究表明，含RfdiC14的脂质体以一种特定且转运蛋白介导的方式在HUVEC、PC3和A431细胞中强烈内化。为了评估RF在体内的靶向潜力，我们制备了一种在RF和脂质之间含有PEG间隔物的两亲化合物——DSPE-PEG-RF。后者成功掺入长循环近红外标记脂质体（直径141±1 nm，PDI 0.07，Zeta电位为-33±1 mV）。在PC3异种移植小鼠中进行的纵向μCT/FMT生物分布研究表明，与对照组相比，DSPE-PEG-RF功能化脂质体的药代动力学特征相似

  DOI：

  10.1021/acs.bioconjchem.6b00317

文献信息

• GLYCERO-COMPOUND HAVING TRIPLE BOND AND MEMBRANE MATERIAL CONTAINING THE SAME
  申请人：BABA Teruhiko

  公开号：US20070105823A1

  公开（公告）日：2007-05-10

  The present invention provides a chemically stable and novel glycero-compound having one or two triple bonds, one molecule of a glycerol and one or two molecules of a fatty alcohol having a triple bond being linked through an ether bond, an organic group being linked to residual hydroxyl groups of the glycerol, which can be used as a membrane material for forming a vesicle membrane due to its high intermolecular cohesive force, and also provides a membrane forming material containing the same. The glycero-compound has a triple bond represented by the following general formula (1): wherein n and m each represents a number of 1 to 17 and the total (n+m) is a number of 4 to 18, n and m may be the same or different, and R represents a hydrogen atom, a metal atom, a phosphoric acid group, or an organic group which may be linked through a phosphoric acid group.

  本发明提供了一种化学稳定且新颖的甘油化合物，其中含有一个或两个三键，一个甘油分子和一个或两个含有三键的脂肪醇分子通过醚键连接，有机基与甘油的残余羟基连接，由于其高分子间内聚力可用作形成囊泡膜的膜材料，还提供了含有相同物质的膜形成材料。该甘油化合物具有以下一般式（1）所代表的三键：其中n和m分别表示1到17之间的数字，总数（n+m）为4到18之间的数字，n和m可以相同也可以不同，R表示氢原子、金属原子、磷酸基或可以通过磷酸基连接的有机基。
• Synthesis and Evaluation of Lysophosphatidylserine Analogues as Inducers of Mast Cell Degranulation. Potent Activities of Lysophosphatidylthreonine and Its 2-Deoxy Derivative
  作者：Masazumi Iwashita、Kumiko Makide、Taro Nonomura、Yoshimasa Misumi、Yuko Otani、Mayuko Ishida、Ryo Taguchi、Masafumi Tsujimoto、Junken Aoki、Hiroyuki Arai、Tomohiko Ohwada

  DOI：10.1021/jm900598m

  日期：2009.10.8

  In response to various exogenous stimuli, mast cells (MCs) release a wide variety of inflammatory mediators stored in their cytoplasmic granules and this release initiates subsequent allergic reactions. Lysophosphatidylserine (lysoPS) has been known as an exogenous inducer to potentiate histamine release from MCs, though even at submicromolar concentrations. In this study, through SAR studies on lysoPS against MC degranulation, we identified lysoPT, a threonine-containing lysophospholipid and its 2-deoxy derivative as novel strong agonists. LysoPT and its 2-deoxy derivative induced histamine release from MCs both in vitro and in vivo at a concentration less than one-tenth that of lysoPS. Notably, lysoPT did not activate a recently proposed lysoPS receptor on MCs, GPR34, demonstrating the presence of another undefined receptor reactive to both lysoPS and lysoPT that is involved in MC degranulation. Thus, the present strong agonists, lysoPT and its 2-deoxy derivative, will be useful tools to understand the mechanisms of lysoPS-induced activation of degranulation of MCs.
• US7777066B2
  申请人：——

  公开号：US7777066B2

  公开（公告）日：2010-08-17
• Structure–Activity Relationships of Lysophosphatidylserine Analogs as Agonists of G-Protein-Coupled Receptors GPR34, P2Y10, and GPR174
  作者：Masaya Ikubo、Asuka Inoue、Sho Nakamura、Sejin Jung、Misa Sayama、Yuko Otani、Akiharu Uwamizu、Keisuke Suzuki、Takayuki Kishi、Akira Shuto、Jun Ishiguro、Michiyo Okudaira、Kuniyuki Kano、Kumiko Makide、Junken Aoki、Tomohiko Ohwada

  DOI：10.1021/jm5020082

  日期：2015.5.28

  Lysophosphatidylserine (LysoPS) is an endogenous lipid mediator generated by hydrolysis of membrane phospholipid phosphatidylserine. Recent ligand screening of orphan G-protein-coupled receptors (GPCRs) identified two LysoPS specific human GPCRs, namely, P2Y10 (LPS2) and GPR174 (LPS3), which, together with previously reported GPR34 (LPS1), comprise a LysoPS receptor family. Herein, we examined the structure-attivity relationships of a series of synthetic LysoPS analogues toward these recently deorphanized LysoPS,receptors, based on the idea that LysoPS can be regarded as consisting of distinct modules (fatty acid, glycerol, and L-Serine) connected by phosphodiester and ester linkages. Starting from the endogenous ligand (1-oleoyl-LysolPS, 1), we optimized the structure of each module and the ester linkage. Accordingly, we identified some structural requirements of each module for potency and for receptor subtype selectivity. Further assembly of individually structure-optimized modules yielded a series of potent and LysoPS receptor subtype-selective agonists, particularly for P2Y10 and GPR174.
• Amphiphilic Phospholipid-Based Riboflavin Derivatives for Tumor Targeting Nanomedicines
  作者：Nataliia Beztsinna、Yoanna Tsvetkova、Matthias Bartneck、Twan Lammers、Fabian Kiessling、Isabelle Bestel

  DOI：10.1021/acs.bioconjchem.6b00317

  日期：2016.9.21

  Riboflavin (RF) is an essential vitamin for cellular metabolism. Recent studies have shown that RF is internalized through RF transporters, which are highly overexpressed by prostate and breast cancer cells, as well as by angiogenic endothelium. Here, we present an optimized synthesis protocol for preparing tailor-made amphiphilic phospholipid-based RF derivatives using phosphoramidite chemistry. The prepared RF amphiphile—RfdiC14—can be inserted into liposome formulations for targeted drug delivery. The obtained liposomes had a hydrodynamic size of 115 ± 5 nm with narrow size distribution (PDI 0.06) and a zeta potential of −52 ± 3 mV. In vitro uptake studies showed that RfdiC14-containing liposomes were strongly internalized in HUVEC, PC3, and A431 cells, in a specific and transporter-mediated manner. To assess the RF targeting potential in vivo, an amphiphile containing PEG spacer between RF and a lipid was prepared—DSPE-PEG-RF. The latter was successfully incorporated into long-circulating near-infrared-labeled liposomes (141 ± 1 nm in diameter, PDI 0.07, zeta potential of −33 ± 1 mV). The longitudinal μCT/FMT biodistribution studies in PC3 xenograft bearing mice demonstrated similar pharmacokinetics profile of DSPE-PEG-RF-functionalized liposomes compared to control. The subsequent histological evaluation of resected tumors revealed higher degree of tumor retention as well as colocalization of targeted liposomes with endothelial cells emphasizing the targeting potential of RF amphiphiles and their utility for the lipid-containing drug delivery systems.

  核黄素（RF）是细胞代谢所必需的维生素。最新研究表明，RF通过RF转运蛋白进行内化，而前列腺癌和乳腺癌细胞以及血管生成内皮细胞中转运蛋白的表达量非常高。在此，我们介绍了一种优化的合成方案，利用亚磷酰胺化学方法制备定制的基于磷脂的RF衍生物。制备的RF两亲化合物——RfdiC14——可以插入脂质体配方中，用于靶向药物递送。所得脂质体的流体动力学尺寸为115±5 nm，尺寸分布窄（PDI 0.06），Zeta电位为-52±3 mV。体外摄取研究表明，含RfdiC14的脂质体以一种特定且转运蛋白介导的方式在HUVEC、PC3和A431细胞中强烈内化。为了评估RF在体内的靶向潜力，我们制备了一种在RF和脂质之间含有PEG间隔物的两亲化合物——DSPE-PEG-RF。后者成功掺入长循环近红外标记脂质体（直径141±1 nm，PDI 0.07，Zeta电位为-33±1 mV）。在PC3异种移植小鼠中进行的纵向μCT/FMT生物分布研究表明，与对照组相比，DSPE-PEG-RF功能化脂质体的药代动力学特征相似