2,3-Di-O-hexadecyl-sn-glycerol 1-phosphate

• 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: 2,3-Di-O-hexadecyl-sn-glycerol 1-phosphate
• 英文别名: [(2R)-2,3-dihexadecoxypropyl] dihydrogen phosphate
• 化学式: C₃₅H₇₃O₆P
• 分子量: 620.935
• InChiKey: MEXBVDOQYYYIGG-PGUFJCEWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  13.7
• 重原子数：
  42
• 可旋转键数：
  36
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1,2-o-二十六基-sn-甘油 在 三乙胺 、 三氯氧磷 作用下， 以 四氯化碳 为溶剂， 以95%的产率得到2,3-Di-O-hexadecyl-sn-glycerol 1-phosphate
  参考文献：
  名称：

  Synthesis of Chiral Diether and Tetraether Phospholipids: Regiospecific Ring Opening of Epoxy Alcohol Intermediates Derived from Asymmetric Epoxidation

  摘要：

  Diether and tetraether phospholipids have been synthesized using chiral epoxy alcohol starting materials (e.g. glycidol 3-nitrobenzenesulfonate esters or tert-butyldiphenylsilyl ethers). These chiral precursors provide control over the stereochemistry, substitution patterns, and steric properties of the phosphoglycerol backbone. Configuration at the sn-2 glycerol carbon was controlled by asymmetric epoxidation of allyl alcohol followed by acid-catalyzed, regioselective: Opening of the oxirane ring using excess aliphatic n-alcohols to give mono-O-alkylated glycerol intermediates in good yields. Nucleophilic attack at the less-hindered carbon of the oxirane ring was highly favored over attack at the sterically less accessible site, typically proceeding with regioselectivities of >10:1 and >95% ee's. Triflic acid, boron trifluoride etherate, toluenesulfonic acid, and tropylium tetrafluoroborate, all at 10 mol %, proved to be the most-effective catalysts compared with 10 % cesium fluoride, 10% magnesium chloride, or 20% DDQ based on (i) comparison of initial rates of product formation, (ii) regioselectivity of attack on the glycidol nucleus, and (iii) isolated yields of 3-O-alkyl-sn-glycerol 1-(3'-nitrobenzenesulfonates). Ether linked phospholipids, produced by alkylation of O-alkylglycerol sulfonates with excess n-alkyl triflates in the presence of equimolar 1,8-bis(dimethylamino)naphthalene, were isolated in 43-49 % overall yields (from glycidol 3-nitrobenzenesulfonate) after tetrabutylammonium hydroxide deprotection and phosphorylation; treatment of the 3-O-alkylglycerol sulfonates with tetrabutylammonium hydroxide prior to alkylation at the sn-2 center led to internal displacement and oxirane ring reformation, rather than hydrolysis to 3-O-alkylglycerol as described in J. Chromatogr. 1990, 506, 611. 3,3'-O-Polymethylene diglycerol phospholipids (bolaamphiphiles) were also prepared by this route using glycidol 3-nitrobenzenesulfonate and bifunctional alpha,omega-diols as nucleophiles. Synthesis of sterically demanding ether lipids, via Sharpless epoxidation of cyclopentene-1-methanol, produced materials that exhibited larger molecular areas than the analogous 1,2-di-O-alkylphosphatidic acids in monolayer experiments, confirming the restricted conformational flexibility of the cyclopentyl derivative at the air-water interface. Bolammphiphiles adopted a U-shaped conformation at the air-water interface. Elution-mode HPLC of racemic 3-O-hexadecyl-2-O-[(3',5'-dinitrophenyl) carbamoyl]glycerol 1-(3'-nitrobenzenesulfonate) on chiral naphthylalanine phases suggests that displacement-mode HPLC (Camacho-Torralba, P. L.; Vigh, G.; Thompson, D. H.; J. Chromatogr. 1993, 641, 31; 1993, 646, 259) may be used to obviate semipreparative chiral syntheses of alkyl glycerol ethers such as platelet activating factors, the antitumor agent ET-18-OCH3, and other biologically active ether lipids.

  DOI：

  10.1021/jo00090a011

文献信息

• US4624919A
  申请人：——

  公开号：US4624919A

  公开（公告）日：1986-11-25
• Synthesis of Chiral Diether and Tetraether Phospholipids: Regiospecific Ring Opening of Epoxy Alcohol Intermediates Derived from Asymmetric Epoxidation
  作者：David H. Thompson、Chris B. Svendsen、Ciro Di Meglio、Valerie C. Anderson

  DOI：10.1021/jo00090a011

  日期：1994.6

  Diether and tetraether phospholipids have been synthesized using chiral epoxy alcohol starting materials (e.g. glycidol 3-nitrobenzenesulfonate esters or tert-butyldiphenylsilyl ethers). These chiral precursors provide control over the stereochemistry, substitution patterns, and steric properties of the phosphoglycerol backbone. Configuration at the sn-2 glycerol carbon was controlled by asymmetric epoxidation of allyl alcohol followed by acid-catalyzed, regioselective: Opening of the oxirane ring using excess aliphatic n-alcohols to give mono-O-alkylated glycerol intermediates in good yields. Nucleophilic attack at the less-hindered carbon of the oxirane ring was highly favored over attack at the sterically less accessible site, typically proceeding with regioselectivities of >10:1 and >95% ee's. Triflic acid, boron trifluoride etherate, toluenesulfonic acid, and tropylium tetrafluoroborate, all at 10 mol %, proved to be the most-effective catalysts compared with 10 % cesium fluoride, 10% magnesium chloride, or 20% DDQ based on (i) comparison of initial rates of product formation, (ii) regioselectivity of attack on the glycidol nucleus, and (iii) isolated yields of 3-O-alkyl-sn-glycerol 1-(3'-nitrobenzenesulfonates). Ether linked phospholipids, produced by alkylation of O-alkylglycerol sulfonates with excess n-alkyl triflates in the presence of equimolar 1,8-bis(dimethylamino)naphthalene, were isolated in 43-49 % overall yields (from glycidol 3-nitrobenzenesulfonate) after tetrabutylammonium hydroxide deprotection and phosphorylation; treatment of the 3-O-alkylglycerol sulfonates with tetrabutylammonium hydroxide prior to alkylation at the sn-2 center led to internal displacement and oxirane ring reformation, rather than hydrolysis to 3-O-alkylglycerol as described in J. Chromatogr. 1990, 506, 611. 3,3'-O-Polymethylene diglycerol phospholipids (bolaamphiphiles) were also prepared by this route using glycidol 3-nitrobenzenesulfonate and bifunctional alpha,omega-diols as nucleophiles. Synthesis of sterically demanding ether lipids, via Sharpless epoxidation of cyclopentene-1-methanol, produced materials that exhibited larger molecular areas than the analogous 1,2-di-O-alkylphosphatidic acids in monolayer experiments, confirming the restricted conformational flexibility of the cyclopentyl derivative at the air-water interface. Bolammphiphiles adopted a U-shaped conformation at the air-water interface. Elution-mode HPLC of racemic 3-O-hexadecyl-2-O-[(3',5'-dinitrophenyl) carbamoyl]glycerol 1-(3'-nitrobenzenesulfonate) on chiral naphthylalanine phases suggests that displacement-mode HPLC (Camacho-Torralba, P. L.; Vigh, G.; Thompson, D. H.; J. Chromatogr. 1993, 641, 31; 1993, 646, 259) may be used to obviate semipreparative chiral syntheses of alkyl glycerol ethers such as platelet activating factors, the antitumor agent ET-18-OCH3, and other biologically active ether lipids.