1-O-octadecyl-2-hydroxy-sn-glycero-3-(2-cyanoethylphospho)-(S)-2,3-O-di-tert-butyldimethylsilyl-glycerol | 1227082-13-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 甘油脂
• 英文名称: 1-O-octadecyl-2-hydroxy-sn-glycero-3-(2-cyanoethylphospho)-(S)-2,3-O-di-tert-butyldimethylsilyl-glycerol
• 英文别名: 1-O-octadecyl-2-hydroxy-sn-glycero-3-(2-cyanoethylphospho)-(S)-2,3-O-di-tertbutyldimethylsilyl-glycerol
• CAS: 1227082-13-4
• 化学式: C₃₉H₈₂NO₈PSi₂
• 分子量: 780.227
• InChiKey: QAMJODCWEUTFPM-ZTIDTZBVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.11
• 重原子数：
  51.0
• 可旋转键数：
  33.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  116.47
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  1-O-octadecyl-2-hydroxy-sn-glycero-3-(2-cyanoethylphospho)-(S)-2,3-O-di-tert-butyldimethylsilyl-glycerol 在 4-二甲氨基吡啶 、 氢氟酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 、 乙腈 为溶剂， 反应 4.67h， 生成
  参考文献：
  名称：

  Synthesis of tocopheryl succinate phospholipid conjugates and monitoring of phospholipase A2 activity

  摘要：

  Tocopheryl succinates (TOSs) are, in contrast to tocopherols, highly cytotoxic against many cancer cells. In this study the enzyme activity of secretory phospholipase A(2) towards various succinate-phospholipid conjugates has been investigated. The synthesis of six novel phospholipids is described, including two TOS phospholipids conjugates. The studies revealed that the TOS conjugates are poor substrates for the enzyme whereas the phospholipids with alkyl and phenyl succinate moieties were hydrolyzed by the enzyme to a high extent. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.024
• 作为产物：
  描述：

  1-O-octadecyl-2-O-(4-methoxybenzyl)-sn-glycero-3-(2-cyanoethylphospho)-(S)-2,3-O-di-tert-butyldimethylsilyl-glycerol 在 水 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以84%的产率得到1-O-octadecyl-2-hydroxy-sn-glycero-3-(2-cyanoethylphospho)-(S)-2,3-O-di-tert-butyldimethylsilyl-glycerol
  参考文献：
  名称：

  Liposomal Formulation of Retinoids Designed for Enzyme Triggered Release

  摘要：

  The design of retinoid phospholipid prodrugs is described based on molecular dynamics simulations and cytotoxicity studies of synthetic retinoid esters. The prodrugs are degradable by secretory phospholipase A(2) IIA and have potential in liposomal drug delivery targeting tumors. We have synthesized four different retinoid phospholipid prodrugs and shown that they form particles in the liposome size region with average diameters of 94-118 nm. Upon subjection to phospholipase A(2), the lipid prodrugs were hydrolyzed, releasing cytotoxic retinoids and lysolipids. The formulated lipid prodrugs displayed IC50 values in the range of 3-19 mu M toward HT-29 and Colo205 colon cancer cells in the presence of phospholipase A(2), while no significant cell death was observed in the absence of the enzyme.

  DOI：

  10.1021/jm100190c

文献信息

• Synthesis and Stability Studies of α,α-Difluoro Ester Phospholipids
  作者：Palle J. Pedersen、Thomas L. Andresen、Mads H. Clausen

  DOI：10.1002/ejoc.201200565

  日期：2012.10.18

  The synthesis of two new α,α-difluoro ester phospholipid conjugates is described and the stability of their liposomal formulations in three different aqueous buffers (pH 4.5, 7.5 and 8.5) has been investigated. The studies confirmed that α,α-difluoro esters are much more prone to hydrolysis when positioned close to the hydrophilic head group of phospholipids than when the functionality is placed in

  描述了两种新的 α,α-二氟酯磷脂结合物的合成，并研究了它们的脂质体制剂在三种不同的水性缓冲液（pH 4.5、7.5 和 8.5）中的稳定性。研究证实，与将官能团置于脂质体双层的亲脂部分相比，α,α-二氟酯在靠近磷脂的亲水性头部基团时更容易水解。这一观察结果进一步支持了通过将制剂作为脂质体膜的一部分来保护可水解功能的概念。
• Synthesis and Biophysical Characterization of Chlorambucil Anticancer Ether Lipid Prodrugs
  作者：Palle J. Pedersen、Mikkel S. Christensen、Tristan Ruysschaert、Lars Linderoth、Thomas L. Andresen、Fredrik Melander、Ole G. Mouritsen、Robert Madsen、Mads H. Clausen

  DOI：10.1021/jm900091h

  日期：2009.5.28

  The synthesis and biophysical characterization of four prodrug ether phospholipid conjugates are described. The lipids are prepared from the anticancer drug chlorambucil and have C16 and C18 ether chains with phosphatidylcholine or phosphatidylglycerol headgroups. All four prodrugs have the ability to form unilamellar liposomes (86-125 nm) and are hydrolyzed by phospholipase A(2), resulting in chlorambucil release. Liposomal formulations of prodrug lipids displayed cytotoxicity toward HT-29, MT-3, and ES-2 cancer cell lines in the presence of phospholipase A(2), with IC50 values in the 8-36 mu M range.
• Prostaglandin phospholipid conjugates with unusual biophysical and cytotoxic properties
  作者：Palle J. Pedersen、Sidsel K. Adolph、Thomas L. Andresen、Mogens W. Madsen、Robert Madsen、Mads H. Clausen

  DOI：10.1016/j.bmcl.2010.06.054

  日期：2010.8

  The synthesis of two secretory phospholipase A(2) IIA sensitive 15-deoxy-Delta(12,14)-prostaglandin J(2) phospholipid conjugates is described and their biophysical and biological properties are reported. The conjugates spontaneously form particles in the liposome size region upon dispersion in an aqueous buffer and both phospholipids are hydrolyzed by phospholipase A(2), but with different conversion rates and extent of hydrolysis. The cytotoxicity was evaluated in HT-29 and Colo205 cells and the conjugates induced cell death in the presence of phospholipase A(2) and surprisingly also in the absence of the enzyme. (C) 2010 Elsevier Ltd. All rights reserved.