O-(2-bromoethyl) O-methyl N-<1',2'-O-isopropylidene-sn-glycero-(3'-N-benzylamino)>phosphoramidate | 160531-80-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: O-(2-bromoethyl) O-methyl N-<1',2'-O-isopropylidene-sn-glycero-(3'-N-benzylamino)>phosphoramidate
• 英文别名: N-benzyl-N-[2-bromoethoxy(methoxy)phosphoryl]-1-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methanamine
• CAS: 160531-80-6
• 化学式: C₁₆H₂₅BrNO₅P
• 分子量: 422.256
• InChiKey: YHLOSZGGDWNEOO-FZADBTJQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  O-(2-bromoethyl) O-methyl N-<1',2'-O-isopropylidene-sn-glycero-(3'-N-benzylamino)>phosphoramidate 在 4-二甲氨基吡啶 、 对甲苯磺酸 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 54.0h， 生成 1,2-O-di-n-hexanoyl-sn-(3-(N-benzylamino)glyceryl)phosphoramidocholine
  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
• 作为产物：
  描述：

  (R)-(-)-对甲基苯磺酸-2,2-二甲基-1,3-二氧戊环基-4-甲酯 在 sodium iodide N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 3.75h， 生成 O-(2-bromoethyl) O-methyl N-<1',2'-O-isopropylidene-sn-glycero-(3'-N-benzylamino)>phosphoramidate
  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

• 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.