(R)-3-Hexanoyloxy-tetradecanoic acid (2R,3R,4R,5S,6R)-2-chloro-5-(diphenoxy-phosphoryloxy)-6-(2,2,2-trichloro-1,1-dimethyl-ethoxycarbonyloxymethyl)-3-(2,2,2-trichloro-ethoxycarbonylamino)-tetrahydro-pyran-4-yl ester | 245515-71-3

• 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: (R)-3-Hexanoyloxy-tetradecanoic acid (2R,3R,4R,5S,6R)-2-chloro-5-(diphenoxy-phosphoryloxy)-6-(2,2,2-trichloro-1,1-dimethyl-ethoxycarbonyloxymethyl)-3-(2,2,2-trichloro-ethoxycarbonylamino)-tetrahydro-pyran-4-yl ester
• 英文别名: [(2R,3R,4R,5S,6R)-2-chloro-5-diphenoxyphosphoryloxy-3-(2,2,2-trichloroethoxycarbonylamino)-6-[(1,1,1-trichloro-2-methylpropan-2-yl)oxycarbonyloxymethyl]oxan-4-yl] (3R)-3-hexanoyloxytetradecanoate
• CAS: 245515-71-3
• 化学式: C₄₆H₆₃Cl₇NO₁₄P
• 分子量: 1133.15
• InChiKey: SRIPBRPCMQMDSI-HWZLOPQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  15.4
• 重原子数：
  69
• 可旋转键数：
  34
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  180
• 氢给体数：
  1
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  (R)-3-Hexanoyloxy-tetradecanoic acid (2R,3R,4R,5S,6R)-2-chloro-5-(diphenoxy-phosphoryloxy)-6-(2,2,2-trichloro-1,1-dimethyl-ethoxycarbonyloxymethyl)-3-(2,2,2-trichloro-ethoxycarbonylamino)-tetrahydro-pyran-4-yl ester 、 Hexanoic acid (R)-1-{[(2R,3R,4R,5S,6R)-2-benzyloxy-5-hydroxy-6-hydroxymethyl-4-(2,2,2-trichloro-ethoxycarbonyloxy)-tetrahydro-pyran-3-ylcarbamoyl]-methyl}-dodecyl ester 在 4 A molecular sieve 、 silver trifluoromethanesulfonate 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 4.0h， 生成 [(2R,3R,4R,5S,6R)-5-diphenoxyphosphoryloxy-2-[[(2R,3S,4R,5R,6R)-5-[[(3R)-3-hexanoyloxytetradecanoyl]amino]-3-hydroxy-6-phenylmethoxy-4-(2,2,2-trichloroethoxycarbonyloxy)oxan-2-yl]methoxy]-3-(2,2,2-trichloroethoxycarbonylamino)-6-[(1,1,1-trichloro-2-methylpropan-2-yl)oxycarbonyloxymethyl]oxan-4-yl] (3R)-3-hexanoyloxytetradecanoate
  参考文献：
  名称：

  3-O-Desacyl Monophosphoryl Lipid A Derivatives:  Synthesis and Immunostimulant Activities

  摘要：

  The synthesis of a series of novel analogues of lipid A, the active principle of lipopolysaccharide, is reported. In these compounds, the 1-O-phosphono and (R)-3-hydroxytetradecanoyl moieties of native Salmonella minnesota R595 lipid A have been replaced with hydrogen and the length of the normal fatty acyl residues has been systematically varied. Normal fatty acid chain length in the 3-O-desacyl monophosphoryl lipid A (MLS) series is shown to be a critical determinant of iNOS gene expression in activated mouse macrophages and the induction of proinflammatory cytokines in human peripheral monocytes. Examination of pyrogenicity in rabbits and lethal toxicity in D-galactosamine-treated mice shows that toxic effects in the MLA series can be ameliorated by modifying fatty acid chain length. When used as an adjuvant for tetanus toroid vaccines, certain MLA derivatives enhance the production of tetanus toroid-specific antibodies in mice.

  DOI：

  10.1021/jm990222b
• 作为产物：
  描述：

  2-(trimethylsilil)ethyl 2-deoxy-4,6-O-isopropylidene-2-(2,2,2-trichloroethoxycarbonylamino)-β-D-glucopyranoside 在 吡啶 、 2-(吡咯烷-1-基)吡啶 、 1,1-二氯甲醚 、 二甲基氨基丙基乙基碳酰胺 、 4-吡咯烷基吡啶 、 溶剂黄146 、 N,N-二异丙基乙胺 、 zinc(II) chloride 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 9.5h， 生成 (R)-3-Hexanoyloxy-tetradecanoic acid (2R,3R,4R,5S,6R)-2-chloro-5-(diphenoxy-phosphoryloxy)-6-(2,2,2-trichloro-1,1-dimethyl-ethoxycarbonyloxymethyl)-3-(2,2,2-trichloro-ethoxycarbonylamino)-tetrahydro-pyran-4-yl ester
  参考文献：
  名称：

  3-O-Desacyl Monophosphoryl Lipid A Derivatives:  Synthesis and Immunostimulant Activities

  摘要：

  The synthesis of a series of novel analogues of lipid A, the active principle of lipopolysaccharide, is reported. In these compounds, the 1-O-phosphono and (R)-3-hydroxytetradecanoyl moieties of native Salmonella minnesota R595 lipid A have been replaced with hydrogen and the length of the normal fatty acyl residues has been systematically varied. Normal fatty acid chain length in the 3-O-desacyl monophosphoryl lipid A (MLS) series is shown to be a critical determinant of iNOS gene expression in activated mouse macrophages and the induction of proinflammatory cytokines in human peripheral monocytes. Examination of pyrogenicity in rabbits and lethal toxicity in D-galactosamine-treated mice shows that toxic effects in the MLA series can be ameliorated by modifying fatty acid chain length. When used as an adjuvant for tetanus toroid vaccines, certain MLA derivatives enhance the production of tetanus toroid-specific antibodies in mice.

  DOI：

  10.1021/jm990222b

文献信息

• Synthesis and biological evaluation of a new class of vaccine adjuvants: aminoalkyl glucosaminide 4-phosphates (AGPs)
  作者：David A. Johnson、C. Gregory Sowell、Craig L. Johnson、Mark T. Livesay、David S. Keegan、Michael J. Rhodes、J. Terry Ulrich、Jon R. Ward、John L. Cantrell、Valerie G. Brookshire

  DOI：10.1016/s0960-894x(99)00374-1

  日期：1999.8

  A novel series of acylated omega-aminoalkyl 2-amino-2-deoxy-4-phosphono-beta-D-glucopyranosides (aminoalkyl glucosaminide 4-phosphates) was synthesized and screened for immunostimulant activity. Several of these compounds enhance the production of tetanus toroid-specific antibodies in mice and augment vaccine-induced cytotoxic T cells against EG.7-ova target cells. (C) 1999 Elsevier Science Ltd. Pill rights reserved.
• 3-<i>O</i>-Desacyl Monophosphoryl Lipid A Derivatives:  Synthesis and Immunostimulant Activities
  作者：David A. Johnson、David S. Keegan、C. Gregory Sowell、Mark T. Livesay、Craig L. Johnson、Lara M. Taubner、Annalivia Harris、Kent R. Myers、Jennifer D. Thompson、Gary L. Gustafson、Michael J. Rhodes、J. Terry Ulrich、Jon R. Ward、Yvonne M. Yorgensen、John L. Cantrell、Valerie G. Brookshire

  DOI：10.1021/jm990222b

  日期：1999.11.1

  The synthesis of a series of novel analogues of lipid A, the active principle of lipopolysaccharide, is reported. In these compounds, the 1-O-phosphono and (R)-3-hydroxytetradecanoyl moieties of native Salmonella minnesota R595 lipid A have been replaced with hydrogen and the length of the normal fatty acyl residues has been systematically varied. Normal fatty acid chain length in the 3-O-desacyl monophosphoryl lipid A (MLS) series is shown to be a critical determinant of iNOS gene expression in activated mouse macrophages and the induction of proinflammatory cytokines in human peripheral monocytes. Examination of pyrogenicity in rabbits and lethal toxicity in D-galactosamine-treated mice shows that toxic effects in the MLA series can be ameliorated by modifying fatty acid chain length. When used as an adjuvant for tetanus toroid vaccines, certain MLA derivatives enhance the production of tetanus toroid-specific antibodies in mice.