3-O-[12-(m-iodophenyl)dodecyl]-2-O-methyl-sn-glycero-1-phosphocholine

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 甘油磷脂
• 英文名称: 3-O-[12-(m-iodophenyl)dodecyl]-2-O-methyl-sn-glycero-1-phosphocholine
• 英文别名: [(2S)-3-[12-(3-iodophenyl)dodecoxy]-2-methoxypropyl] 2-(trimethylazaniumyl)ethyl phosphate
• 化学式: C₂₇H₄₉INO₆P
• 分子量: 641.567
• InChiKey: ZSEKDUVBISKQAJ-MHZLTWQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  36
• 可旋转键数：
  23
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  77
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-O-(p-methoxybenzyl)-2-O-methyl-3-O-<12-(m-iodophenyl)dodecyl>-sn-glycerol 在 三氯化铝 、 苯甲醚 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 40.75h， 生成 3-O-[12-(m-iodophenyl)dodecyl]-2-O-methyl-sn-glycero-1-phosphocholine
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Radioiodinated Phospholipid Ether Stereoisomers

  摘要：

  Radioiodinated phospholipid ethers have shown the remarkable ability to selectively accumulate in a variety of animal tumors as well as in human tumor xenografts. It has been suggested that this tumor avidity may arise as a consequence of metabolic differences between tumor and corresponding normal tissue. One such compound, 1-O-[12-(m-iodophenyl)dodecyl]-2-O-methyl-rac-glycero- 3-phosphocholine (NM-294), contains a chiral center at the sn-2 position. The unnatural S- and natural R-enantiomers (4 and 5, respectively) of NM-294 were synthesized in order to provide further information on the mechanism(s) responsible for the tumor avidity of phospholipid ethers. In vitro cytotoxicity studies demonstrated a lack of stereospecificity. Biodistribution studies in rats bearing the Walker 256 tumor demonstrated the S- and R-isomers to have similar tissue uptake at 24 and 48 h after administration. Tumor-to-blood ratios at 24 h were 11.1 and 11.0 for the S- and R-isomers, respectively. In addition, gamma-camera scintigrams of tumor-bearing rats at various time points after iv administration of the S- and R-isomers did not show any qualitative differences in the distribution of radioactivity. Prior studies have shown that rac-NM-294 was not a substrate for phosphatidylcholine specific phospholipase C, but was a substrate for two forms of phospholipase D (PLD). Therefore, metabolism studies with 4 and 5 with various forms of PLD were performed. PLD from cabbage demonstrated a degree of stereoselectivity. In the presence of 1% ethanol, the R-isomer was metabolized to the greatest extent, followed by rac-NM-294 and the S-isomer. PLD isolated from Streptomyces chromofuscus failed to demonstrate any stereoselectivity. The results suggest that the mechanism(s) of retention of these compounds in tumors may not involve a highly stereoselective component.

  DOI：

  10.1021/jm00016a019

文献信息

• Synthesis and Biological Evaluation of Radioiodinated Phospholipid Ether Stereoisomers
  作者：Mark A. Rampy、Anatoly N. Pinchuk、Jamey P. Weichert、R. W. Scott Skinner、Susan J. Fisher、Richard L. Wahl、Milton D. Gross、Raymond E. Counsell

  DOI：10.1021/jm00016a019

  日期：1995.8

  Radioiodinated phospholipid ethers have shown the remarkable ability to selectively accumulate in a variety of animal tumors as well as in human tumor xenografts. It has been suggested that this tumor avidity may arise as a consequence of metabolic differences between tumor and corresponding normal tissue. One such compound, 1-O-[12-(m-iodophenyl)dodecyl]-2-O-methyl-rac-glycero- 3-phosphocholine (NM-294), contains a chiral center at the sn-2 position. The unnatural S- and natural R-enantiomers (4 and 5, respectively) of NM-294 were synthesized in order to provide further information on the mechanism(s) responsible for the tumor avidity of phospholipid ethers. In vitro cytotoxicity studies demonstrated a lack of stereospecificity. Biodistribution studies in rats bearing the Walker 256 tumor demonstrated the S- and R-isomers to have similar tissue uptake at 24 and 48 h after administration. Tumor-to-blood ratios at 24 h were 11.1 and 11.0 for the S- and R-isomers, respectively. In addition, gamma-camera scintigrams of tumor-bearing rats at various time points after iv administration of the S- and R-isomers did not show any qualitative differences in the distribution of radioactivity. Prior studies have shown that rac-NM-294 was not a substrate for phosphatidylcholine specific phospholipase C, but was a substrate for two forms of phospholipase D (PLD). Therefore, metabolism studies with 4 and 5 with various forms of PLD were performed. PLD from cabbage demonstrated a degree of stereoselectivity. In the presence of 1% ethanol, the R-isomer was metabolized to the greatest extent, followed by rac-NM-294 and the S-isomer. PLD isolated from Streptomyces chromofuscus failed to demonstrate any stereoselectivity. The results suggest that the mechanism(s) of retention of these compounds in tumors may not involve a highly stereoselective component.