N-(2,3-二羟基丙基)十四烷酰胺 | 35179-73-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: N-(2,3-二羟基丙基)十四烷酰胺
• 英文名称: 3-myristoylamino-1,2-propanediol
• 英文别名: Tetradecanamide, N-(2,3-dihydroxypropyl)-；N-(2,3-dihydroxypropyl)tetradecanamide
• CAS: 35179-73-8
• 化学式: C₁₇H₃₅NO₃
• 分子量: 301.47
• InChiKey: LYMFTXTXMIUQPP-UHFFFAOYSA-N

物化性质

• 沸点：
  503.7±40.0 °C(Predicted)
• 密度：
  0.970±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  21
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(2,3-二羟基丙基)十四烷酰胺 在 吡啶 、 甲醇 、 sodium hydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 28.0h， 生成 Phosphoric acid 2-bromo-ethyl ester 2-ethoxy-3-tetradecanoylamino-propyl ester
  参考文献：
  名称：

  Structure−Activity Relationship for Enhancement of Paracellular Permeability across Caco-2 Cell Monolayers by 3-Alkylamido-2-alkoxypropylphosphocholines

  摘要：

  Paracellular permeability enhancers have been used to improve the oral bioavailability of hydrophilic drugs; however, the mechanism of action of many enhancers is poorly understood. In this study, highly potent enhancers of paracellular permeability were identified in the 3-alkylamido-2-alkoxypropylphosphocholine series, and a structure-activity relationship was developed for enhancement of paracellular permeability across Caco-2 cell monolayers. Compounds with short (<5 carbons) hydrocarbon chains at both C-2 and C-3 were generally inactive. The potency exhibited a parabolic relationship with respect to the chain length at either C-2 or C-3. Linear molecules (i.e., compounds with a short hydrocarbon chain at C-2 or C-3 and a long hydrocarbon chain on C-3 or C-2, respectively) were more potent than the corresponding branched molecules with the same carbon load. The efficacy of 3-alkylamido2-alkoxypropylphosphocholines as enhancers of paracellular permeability was not dependent on their existence in micellar form or their ability to alter the fluidity of cell membrane. Previously, a correlation-between the potency of alkylphosphocholines as enhancers of paracellular permeability and the inhibitors of phospholipase C (PLC) was established in Madine Darby canine kidney (MDCK) cell monolayers. The potencies of selected 3-alkylamido-2-alkoxypropylphosphocholines as inhibitors of PLC and enhancers of paracellular permeability fit well into this correlation. Therefore, phosphocholines are likely to increase paracellular permeability by modulating the signal transduction pathway initiated by a PLC-catalyzed reaction rather than by physically altering the cell membrane.

  DOI：

  10.1021/jm020001x
• 作为产物：
  描述：

  3-氨基-1,2-丙二醇 、 肉豆蔻酰氯 在 吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 N-(2,3-二羟基丙基)十四烷酰胺
  参考文献：
  名称：

  Structure−Activity Relationship for Enhancement of Paracellular Permeability across Caco-2 Cell Monolayers by 3-Alkylamido-2-alkoxypropylphosphocholines

  摘要：

  Paracellular permeability enhancers have been used to improve the oral bioavailability of hydrophilic drugs; however, the mechanism of action of many enhancers is poorly understood. In this study, highly potent enhancers of paracellular permeability were identified in the 3-alkylamido-2-alkoxypropylphosphocholine series, and a structure-activity relationship was developed for enhancement of paracellular permeability across Caco-2 cell monolayers. Compounds with short (<5 carbons) hydrocarbon chains at both C-2 and C-3 were generally inactive. The potency exhibited a parabolic relationship with respect to the chain length at either C-2 or C-3. Linear molecules (i.e., compounds with a short hydrocarbon chain at C-2 or C-3 and a long hydrocarbon chain on C-3 or C-2, respectively) were more potent than the corresponding branched molecules with the same carbon load. The efficacy of 3-alkylamido2-alkoxypropylphosphocholines as enhancers of paracellular permeability was not dependent on their existence in micellar form or their ability to alter the fluidity of cell membrane. Previously, a correlation-between the potency of alkylphosphocholines as enhancers of paracellular permeability and the inhibitors of phospholipase C (PLC) was established in Madine Darby canine kidney (MDCK) cell monolayers. The potencies of selected 3-alkylamido-2-alkoxypropylphosphocholines as inhibitors of PLC and enhancers of paracellular permeability fit well into this correlation. Therefore, phosphocholines are likely to increase paracellular permeability by modulating the signal transduction pathway initiated by a PLC-catalyzed reaction rather than by physically altering the cell membrane.

  DOI：

  10.1021/jm020001x

文献信息

• Continuous lipase-catalyzed production of pseudo-ceramides in a packed-bed bioreactor
  作者：Florian Le Joubioux、Nicolas Bridiau、Mehdi Sanekli、Marianne Graber、Thierry Maugard

  DOI：10.1016/j.molcatb.2014.08.022

  日期：2014.11

  a two-step continuous enzymatic process with immobilized Candida antarctica lipase B (Novozym® 435) in a packed-bed bioreactor. The first step involved the selective N-acylation of 3-amino-1,2-propanediol using stearic acid as the first acyl donor (i). This was followed by the selective O-acylation of the N-stearyl 3-amino-1,2-propanediol synthesized in the first step, with myristic acid as the second

  神经酰胺是鞘脂化合物，在制药和化妆品工业中作为活性成分都非常有吸引力。在这项研究中，神经酰胺类似物的合成，即所谓的伪神经酰胺，进行了使用首次与固定的两步连续酶促过程念珠菌antarcti CA脂肪酶B（诺维信®在填充床435）生物反应器。第一步涉及使用硬脂酸作为第一酰基供体（i）对3-氨基-1，2-丙二醇进行选择性N-酰化。随后是第一步中合成的N-硬脂基3-氨基-1,2-丙二醇的选择性O-酰化反应，以肉豆蔻酸作为第二个酰基供体，生成N，O-二酰基3-氨基-1，2-丙二醇型假神经酰胺，即1- O-肉豆蔻基，3- N-硬脂基3-氨基-1，2-丙二醇（ii）。首先通过评估三个因素的影响对工艺进行优化：进料流速，生物催化剂的量和底物浓度。在最佳条件下，酰胺合成产率为92％，令人满意的生产率为3.15 mmol h -1  g生物催化剂-1（1128 mg h -1  g生物催化剂-1）。第二步，N-酰基3-氨基-1
• US4070309A
  申请人：——

  公开号：US4070309A

  公开（公告）日：1978-01-24
• US4297251A
  申请人：——

  公开号：US4297251A

  公开（公告）日：1981-10-27
• US7344868B2
  申请人：——

  公开号：US7344868B2

  公开（公告）日：2008-03-18
• Structure−Activity Relationship for Enhancement of Paracellular Permeability across Caco-2 Cell Monolayers by 3-Alkylamido-2-alkoxypropylphosphocholines
  作者：Hui Ouyang、Susan L. Morris-Natschke、Khalid S. Ishaq、Peter Ward、Dongzhou Liu、Sarah Leonard、Dhiren R. Thakker

  DOI：10.1021/jm020001x

  日期：2002.6.1

  Paracellular permeability enhancers have been used to improve the oral bioavailability of hydrophilic drugs; however, the mechanism of action of many enhancers is poorly understood. In this study, highly potent enhancers of paracellular permeability were identified in the 3-alkylamido-2-alkoxypropylphosphocholine series, and a structure-activity relationship was developed for enhancement of paracellular permeability across Caco-2 cell monolayers. Compounds with short (<5 carbons) hydrocarbon chains at both C-2 and C-3 were generally inactive. The potency exhibited a parabolic relationship with respect to the chain length at either C-2 or C-3. Linear molecules (i.e., compounds with a short hydrocarbon chain at C-2 or C-3 and a long hydrocarbon chain on C-3 or C-2, respectively) were more potent than the corresponding branched molecules with the same carbon load. The efficacy of 3-alkylamido2-alkoxypropylphosphocholines as enhancers of paracellular permeability was not dependent on their existence in micellar form or their ability to alter the fluidity of cell membrane. Previously, a correlation-between the potency of alkylphosphocholines as enhancers of paracellular permeability and the inhibitors of phospholipase C (PLC) was established in Madine Darby canine kidney (MDCK) cell monolayers. The potencies of selected 3-alkylamido-2-alkoxypropylphosphocholines as inhibitors of PLC and enhancers of paracellular permeability fit well into this correlation. Therefore, phosphocholines are likely to increase paracellular permeability by modulating the signal transduction pathway initiated by a PLC-catalyzed reaction rather than by physically altering the cell membrane.