perdeuteroazone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: perdeuteroazone
• 英文别名: dodecyl-azacycloheptanone-d35；3,3,4,4,5,5,6,6,7,7-Decadeuterio-1-(1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12,12-pentacosadeuteriododecyl)azepan-2-one
• 化学式: C₁₈H₃₅NO
• 分子量: 316.204
• InChiKey: AXTGDCSMTYGJND-KNAXIHRDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  20
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  月桂酸-d23 在 吡啶 、 lithium aluminium deuteride 、 三溴化磷 、 sodium hydride 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 26.5h， 生成 perdeuteroazone
  参考文献：
  名称：

  2H NMR evidence for dynamic disorder in human skin induced by the penetration enhancer azone

  摘要：

  Penetration enhancers mediate trans-dermal drug delivery. The penetration enhancer dodecyl-azacycloheptanone (Azone(R)) was characterized in situ with H-2 NMR on human stratum corneum treated with either uniformly deuterated Azone(R) or penetration enhancer with only the entire chain deuterated, in both cases in propylene glycol. The H-2 NMR spectrum at ambient temperature constitutes a single narrow line only 180 Hz wide. This contrasts with the complex lineshapes 1-25 kHz wide commonly observed for methylene deuterons of lipids in a bilayer gel phase, Hence there is no evidence for differences in orientational behaviour between different deuterons at ambient temperature. The narrow line translates into a low overall order parameter S-CD < 0.0008, for all deuterons, revealing rapid motion of the entire enhancer with correlation times tau(c) much less than 6 x 10(-6) s, in all possible directions. At temperatures of about 150 K a H-2 NMR pattern characteristic for a random isotropic powder was observed on samples of stacked stratum corneum sheets at different orientations with respect to the magnetic field. This provides strong evidence for random isotropic freezing of the Azone(R) molecules upon cooling. The H-2 NMR data suggest than incubation with Azone(R) in propylene glycol provokes dynamic structural disorder of the intercellular lamellar lipid structure throughout the stratum corneum and possibly even the creation of fluid domains involving the intercellular lipids, which may be essential for the penetration enhancing effect.

  DOI：

  10.1016/0584-8539(96)01680-7

文献信息

• The synthesis of perdeuterated azone (d35-1-dodecylhexahydro-2H-azepin-2-one)
  作者：Paul W. Groundwater、Jonathan Hadgraft、Julian E. Harrison、Adam C. Watkinson

  DOI：10.1002/jlcr.2580341107

  日期：1994.11

  Perdeuteroazone (3) has been synthesised via the base-catalysed coupling of d11-hexahydro-2H-azepin-2-one (2) with d25-1-chlorododecane.

  Perdeuteroazone (3) 是通过 d11-六氢-2H-呋喃-2-酮 (2) 与 d25-1-氯十二烷的碱催化偶联合成的。
• Groundwater Paul W., Hadgraft Jonathan, Harrison Julian E., Watkinson Ada+, J. Labell. Compounds and Radiopharm, 34 (1994) N 11, S 1047-1053
  作者：Groundwater Paul W., Hadgraft Jonathan, Harrison Julian E., Watkinson Ada+

  DOI：——

  日期：——
• 2H NMR evidence for dynamic disorder in human skin induced by the penetration enhancer azone
  作者：F.R. Bezema、E. Marttin、P.E.H. Roemelé、J. Brussee、H.E. Boddé、H.J.M. de Groot

  DOI：10.1016/0584-8539(96)01680-7

  日期：1996.7

  Penetration enhancers mediate trans-dermal drug delivery. The penetration enhancer dodecyl-azacycloheptanone (Azone(R)) was characterized in situ with H-2 NMR on human stratum corneum treated with either uniformly deuterated Azone(R) or penetration enhancer with only the entire chain deuterated, in both cases in propylene glycol. The H-2 NMR spectrum at ambient temperature constitutes a single narrow line only 180 Hz wide. This contrasts with the complex lineshapes 1-25 kHz wide commonly observed for methylene deuterons of lipids in a bilayer gel phase, Hence there is no evidence for differences in orientational behaviour between different deuterons at ambient temperature. The narrow line translates into a low overall order parameter S-CD < 0.0008, for all deuterons, revealing rapid motion of the entire enhancer with correlation times tau(c) much less than 6 x 10(-6) s, in all possible directions. At temperatures of about 150 K a H-2 NMR pattern characteristic for a random isotropic powder was observed on samples of stacked stratum corneum sheets at different orientations with respect to the magnetic field. This provides strong evidence for random isotropic freezing of the Azone(R) molecules upon cooling. The H-2 NMR data suggest than incubation with Azone(R) in propylene glycol provokes dynamic structural disorder of the intercellular lamellar lipid structure throughout the stratum corneum and possibly even the creation of fluid domains involving the intercellular lipids, which may be essential for the penetration enhancing effect.