(2R,4S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl [2-octadecanoylthio-3-(octadecyloxy)prop-1-yl] methyl phosphate | 1186291-18-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (2R,4S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl [2-octadecanoylthio-3-(octadecyloxy)prop-1-yl] methyl phosphate
• CAS: 1186291-18-8
• 化学式: C₄₆H₉₁O₈PS
• 分子量: 835.263
• InChiKey: BVDVMNHSJAZOBV-FIJGBCNWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  15.09
• 重原子数：
  56.0
• 可旋转键数：
  43.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.98
• 拓扑面积：
  89.52
• 氢给体数：
  0.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  (2R,4S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl [2-octadecanoylthio-3-(octadecyloxy)prop-1-yl] methyl phosphate 在 水 、 三甲胺 、 盐酸 作用下， 以 二氯甲烷 、 异丙醇 、 乙腈 、 甲醇 为溶剂， 以65%的产率得到2,3-dihydroxyprop-1-yl [2-octadecanoylthio-3-(octadecyloxy)prop-1-yl] phosphate
  参考文献：
  名称：

  Mechanistic Study of the sPLA₂-Mediated Hydrolysis of a Thio-ester Pro Anticancer Ether Lipid

  摘要：

  Secretory phospholipase A(2) (sPLA(2)) is an interesting enzyme for triggered liposomal drug delivery to tumor tissue due the overexpression of sPLA(2) in cancerous tissue. A drug delivery system based on the triggered release of therapeutics from sPLA(2)-sensitive liposomes constituted of pro anticancer ether lipids, which become cytotoxic upon sPLA(2)-catalyzed hydrolysis has previously been established. To optimize the hydrolysis rate of the lipids and thereby optimizing the release profile of the drugs from the liposomes, we have synthesized a thio-ester pro anticancer ether lipid. Liposomes constituted of this lipid showed an altered rate of hydrolysis by sPLA(2). We have tested the cytotoxicity of the thio-ester pro anticancer ether lipids toward cancer cells, and the results showed that the cytotoxicity is indeed maintained upon sPLA(2) exposure. To further understand the origin for the observed different hydrolysis rates for the esters, we have applied molecular dynamics simulations and density functional theory. The combination of these theoretical methods has given valuable insight into the molecular mechanism for sPLA(2) action on sulfur-containing phospholipids. It appears that the enzyme-catalyzed hydrolysis of thio-esters follow a different pathway compared to the hydrolysis pathway of the free thio-ester.

  DOI：

  10.1021/ja901412j
• 作为产物：
  描述：

  在 叔丁基过氧化氢 作用下， 以 癸烷 、 二氯甲烷 为溶剂， 反应 1.5h， 以66 mg的产率得到(2R,4S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl [2-octadecanoylthio-3-(octadecyloxy)prop-1-yl] methyl phosphate
  参考文献：
  名称：

  Mechanistic Study of the sPLA₂-Mediated Hydrolysis of a Thio-ester Pro Anticancer Ether Lipid

  摘要：

  Secretory phospholipase A(2) (sPLA(2)) is an interesting enzyme for triggered liposomal drug delivery to tumor tissue due the overexpression of sPLA(2) in cancerous tissue. A drug delivery system based on the triggered release of therapeutics from sPLA(2)-sensitive liposomes constituted of pro anticancer ether lipids, which become cytotoxic upon sPLA(2)-catalyzed hydrolysis has previously been established. To optimize the hydrolysis rate of the lipids and thereby optimizing the release profile of the drugs from the liposomes, we have synthesized a thio-ester pro anticancer ether lipid. Liposomes constituted of this lipid showed an altered rate of hydrolysis by sPLA(2). We have tested the cytotoxicity of the thio-ester pro anticancer ether lipids toward cancer cells, and the results showed that the cytotoxicity is indeed maintained upon sPLA(2) exposure. To further understand the origin for the observed different hydrolysis rates for the esters, we have applied molecular dynamics simulations and density functional theory. The combination of these theoretical methods has given valuable insight into the molecular mechanism for sPLA(2) action on sulfur-containing phospholipids. It appears that the enzyme-catalyzed hydrolysis of thio-esters follow a different pathway compared to the hydrolysis pathway of the free thio-ester.

  DOI：

  10.1021/ja901412j