1,2-O-di-n-hexanoyl-sn-3'-glycero-3(R_P/S_P)-phosphocholine | 160636-77-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 甘油-3-硫代磷酸胆碱
• 英文名称: 1,2-O-di-n-hexanoyl-sn-3'-glycero-3(R_P/S_P)-phosphocholine
• 英文别名: 2-[[(2R)-2,3-di(hexanoyloxy)propoxy]-oxidophosphinothioyl]oxyethyl-trimethylazanium
• CAS: 160636-77-1
• 化学式: C₂₀H₄₀NO₇PS
• 分子量: 469.58
• InChiKey: HQJXUFIDYYTPQL-QHSQBYJISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  30
• 可旋转键数：
  20
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  126
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1,2-O-di-n-hexanoyl-sn-3'-glycero-3(R_P/S_P)-phosphocholine 在 吡啶 、 4-二甲氨基吡啶 作用下， 以 乙醚 、 氯仿 为溶剂， 反应 20.0h， 生成 1,2-di-n-hexanoyl-sn-glycero-3(R_p)-phosphothiocholine
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Phospholipid Analogs as Inhibitors of the Bacterial Phospholipase C from Bacillus cereus

  摘要：

  Enzymes belonging to the phospholipase C (PLC) family hydrolyze the phosphodiester bond of phospholipids to give a diacylglycerol and a phosphorylated head group. The bacterial phospholipase C from Bacillus cereus (PLC(Bc)) has been studied extensively, and there is a wealth of information regarding those structural features that are important for substrate activity. In contrast, there is virtually no data available regarding structure-activity relationships for inhibitors of this enzyme. To address this shortcoming, a series of optically pure analogues of 1,2-dihexanoyl-sn-glycero-3-phosphocholine (2) containing different replacements of the phosphate group were first synthesized including the phosphoramidates 4 and 8, the phosphonate 5, the (difluoromethylene)phosphonate 6, the thiophosphate 7, the diastereomeric phosphorothioates 9 and 10, and the phosphorodithioate 11. Each of these phosphatidylcholine derivatives was tested for inhibitor or substrate activity with PLC(Bc) using the water-soluble phosphatidylcholine 2 as the monomeric substrate. The measurements were conducted below the critical micellar concentrations of both 2 and the inhibitor. Of the analogues, only 7 and 9 underwent observable enzymatic hydrolysis under the assay conditions used. The k(cat) of the (Sp)-phosphorothioate 9 was approximately one-fifth that of 2, and when compared to 2, 7 was hydrolyzed only very slowly by the enzyme. Kinetic studies indicated that the phospholipid analogues tested were competitive inhibitors with increasing K-i's follows: 7 approximate to 11 approximate to 10 < 4 approximate to 8 < 5 approximate to 6.

  DOI：

  10.1021/jo00096a024
• 作为产物：
  描述：

  己酸 在 palladium on activated charcoal 吡啶 、 1,2,3,4,5,6,7,8-八硫杂环辛烷 、 4-二甲氨基吡啶 、 氢氟酸 、 氢气 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 吡啶 、 乙醇 、 二氯甲烷 、 溶剂黄146 、 甲苯 为溶剂， 反应 63.0h， 生成 1,2-O-di-n-hexanoyl-sn-3'-glycero-3(R_P/S_P)-phosphocholine
  参考文献：
  名称：

  General Method for the Synthesis of Phospholipid Derivatives of 1,2-O-Diacyl-sn-Glycerols

  摘要：

  An efficient phosphite coupling protocol is described for the syntheses of the major classes of phospholipids that are derived from 1,2-O-diacyl-sn-glycerols and analogues thereof. The symmetrical diacyl glycerols 10c,d were prepared by straightforward acylation of 3-O-benzyl-sn-glycerol (7) with the appropriate carboxylic acid in the presence of dicyclohexylcarbodiimide (DCC) and 4-(dimethylamino)pyridine (DMAP). A simple method for preparing saturated and unstaturated mixed 1,2-O-diacyl-sn-glycerols was then devised that involved stepwise acylation of 7 with different alkyl carboxylic acids and debenzylation this procedure is exemplified by the preparation of 10a,b. The 1,2-O-diacyl-sn-glycerols 10a-d were then coupled with suitably protected lipid head groups employing reactive alkyl or aryl dichlorophosphites to give intermediate phosphite triesters in high overall yields. Oxidation or sulfurization of these phosphites proceeded smoothly to give the corresponding phosphate or phosphorothioate triesters, deprotection of which then provided the phosphatidylcholines 16 and 17, the phosphatidylethanolamine 20, the phosphatidylserine 28, and the phosphatidylinositols 37 and 38. Preparation of 37 and 38 required the invention of an improved method for resolving the isopropylidene-protected D-myo-inositol derivative 33. This phosphite coupling procedure was modified to assemble phospholipids bearing-polyunsaturated acyl side chains at the sn-2-position as exemplified by the preparation of the phosphatidylethanolamine 26. The one-pot phosphite coupling procedure is also applicable to the syntheses of a variety of other biologically interesting phospholipid analogues. For example, the phosphatidylinositol analogues 49-51, in which the hydroxyl group at C(2) of the inositol ring has been modified, were prepared in excellent overall yields by conjoining the 1,2-O-diacyl-sn-glycerol 10c with the protected inositol derivatives 44, 45, and 48. Phospholipid analogues that contain other replacements of the phosphate group including phosphoramidates and thiophosphates maybe prepared as evidenced by the syntheses of 56 and 61 in which the sn-3 oxygen atom of the 1,2-O-diacyl-sn-glycerol moiety is replaced with an N-benzyl group or a sulfur atom, respectively.

  DOI：

  10.1021/jo00096a023

文献信息

• Design, Synthesis, and Evaluation of Phospholipid Analogs as Inhibitors of the Bacterial Phospholipase C from Bacillus cereus
  作者：Stephen F. Martin、Yue-Ling Wong、Allan S. Wagman

  DOI：10.1021/jo00096a024

  日期：1994.8

  Enzymes belonging to the phospholipase C (PLC) family hydrolyze the phosphodiester bond of phospholipids to give a diacylglycerol and a phosphorylated head group. The bacterial phospholipase C from Bacillus cereus (PLC(Bc)) has been studied extensively, and there is a wealth of information regarding those structural features that are important for substrate activity. In contrast, there is virtually no data available regarding structure-activity relationships for inhibitors of this enzyme. To address this shortcoming, a series of optically pure analogues of 1,2-dihexanoyl-sn-glycero-3-phosphocholine (2) containing different replacements of the phosphate group were first synthesized including the phosphoramidates 4 and 8, the phosphonate 5, the (difluoromethylene)phosphonate 6, the thiophosphate 7, the diastereomeric phosphorothioates 9 and 10, and the phosphorodithioate 11. Each of these phosphatidylcholine derivatives was tested for inhibitor or substrate activity with PLC(Bc) using the water-soluble phosphatidylcholine 2 as the monomeric substrate. The measurements were conducted below the critical micellar concentrations of both 2 and the inhibitor. Of the analogues, only 7 and 9 underwent observable enzymatic hydrolysis under the assay conditions used. The k(cat) of the (Sp)-phosphorothioate 9 was approximately one-fifth that of 2, and when compared to 2, 7 was hydrolyzed only very slowly by the enzyme. Kinetic studies indicated that the phospholipid analogues tested were competitive inhibitors with increasing K-i's follows: 7 approximate to 11 approximate to 10 < 4 approximate to 8 < 5 approximate to 6.
• General Method for the Synthesis of Phospholipid Derivatives of 1,2-O-Diacyl-sn-Glycerols
  作者：Stephen F. Martin、John A. Josey、Yue-Ling Wong、Daniel W. Dean

  DOI：10.1021/jo00096a023

  日期：1994.8

  An efficient phosphite coupling protocol is described for the syntheses of the major classes of phospholipids that are derived from 1,2-O-diacyl-sn-glycerols and analogues thereof. The symmetrical diacyl glycerols 10c,d were prepared by straightforward acylation of 3-O-benzyl-sn-glycerol (7) with the appropriate carboxylic acid in the presence of dicyclohexylcarbodiimide (DCC) and 4-(dimethylamino)pyridine (DMAP). A simple method for preparing saturated and unstaturated mixed 1,2-O-diacyl-sn-glycerols was then devised that involved stepwise acylation of 7 with different alkyl carboxylic acids and debenzylation this procedure is exemplified by the preparation of 10a,b. The 1,2-O-diacyl-sn-glycerols 10a-d were then coupled with suitably protected lipid head groups employing reactive alkyl or aryl dichlorophosphites to give intermediate phosphite triesters in high overall yields. Oxidation or sulfurization of these phosphites proceeded smoothly to give the corresponding phosphate or phosphorothioate triesters, deprotection of which then provided the phosphatidylcholines 16 and 17, the phosphatidylethanolamine 20, the phosphatidylserine 28, and the phosphatidylinositols 37 and 38. Preparation of 37 and 38 required the invention of an improved method for resolving the isopropylidene-protected D-myo-inositol derivative 33. This phosphite coupling procedure was modified to assemble phospholipids bearing-polyunsaturated acyl side chains at the sn-2-position as exemplified by the preparation of the phosphatidylethanolamine 26. The one-pot phosphite coupling procedure is also applicable to the syntheses of a variety of other biologically interesting phospholipid analogues. For example, the phosphatidylinositol analogues 49-51, in which the hydroxyl group at C(2) of the inositol ring has been modified, were prepared in excellent overall yields by conjoining the 1,2-O-diacyl-sn-glycerol 10c with the protected inositol derivatives 44, 45, and 48. Phospholipid analogues that contain other replacements of the phosphate group including phosphoramidates and thiophosphates maybe prepared as evidenced by the syntheses of 56 and 61 in which the sn-3 oxygen atom of the 1,2-O-diacyl-sn-glycerol moiety is replaced with an N-benzyl group or a sulfur atom, respectively.