(3aS,6S,6aS)-3-benzyl-6-octyltetrahydrofuro[3,4-d][1,3]oxazol-2(3H)-one | 943061-00-5

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: (3aS,6S,6aS)-3-benzyl-6-octyltetrahydrofuro[3,4-d][1,3]oxazol-2(3H)-one
• CAS: 943061-00-5
• 化学式: C₂₀H₂₉NO₃
• 分子量: 331.455
• InChiKey: UHDMEQUXWLIHRD-FHWLQOOXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.53
• 重原子数：
  24.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  38.77
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (3aS,6S,6aS)-3-benzyl-6-octyltetrahydrofuro[3,4-d][1,3]oxazol-2(3H)-one 在 sodium 作用下， 以 四氢呋喃 、 氨 为溶剂， 反应 4.0h， 以83%的产率得到(3aS,6S,6aS)-6-octyltetrahydrofuro[3,4-d][1,3]oxazol-2(3H)-one
  参考文献：
  名称：

  Enantioselective access to a versatile 4-oxazolidinonecarbaldehyde and application to the synthesis of a cytotoxic jaspine B truncated analogue

  摘要：

  The preparation of the versatile aldehyde 15 via a concise route based on a formal anti-asymmetric aminohydroxylation and its use in a 5-step synthesis of a cytotoxic C-12 analogue of the natural anhydrophytosphingosine jaspine B is presented. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2007.03.029
• 作为产物：
  描述：

  正辛基镁溴盐 在 palladium dihydroxide cerium(III) chloride 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 二氯甲烷 为溶剂， -78.0~20.0 ℃ 、1.0 MPa 条件下， 反应 56.42h， 生成 (3aS,6S,6aS)-3-benzyl-6-octyltetrahydrofuro[3,4-d][1,3]oxazol-2(3H)-one
  参考文献：
  名称：

  Enantioselective access to a versatile 4-oxazolidinonecarbaldehyde and application to the synthesis of a cytotoxic jaspine B truncated analogue

  摘要：

  The preparation of the versatile aldehyde 15 via a concise route based on a formal anti-asymmetric aminohydroxylation and its use in a 5-step synthesis of a cytotoxic C-12 analogue of the natural anhydrophytosphingosine jaspine B is presented. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2007.03.029

文献信息

• Flexible and enantioselective access to jaspine B and biologically active chain-modified analogues thereof
  作者：Yahya Salma、Stéphanie Ballereau、Carine Maaliki、Sonia Ladeira、Nathalie Andrieu-Abadie、Yves Génisson

  DOI：10.1039/c004218h

  日期：——

  Whereas the all-cis tetrahydrofuran framework of the cytotoxic anhydrophytosphingosine jaspine B is considered as a relevant pharmacophore, little is known about the influence of the aliphatic chain of this amphiphilic molecule on its activity. We developed a synthetic strategy allowing flexible introduction of various lipophilic fragments in the jaspine's skeleton. The route was validated with two distinct approaches to jaspine B. Five chain-modified analogues were also prepared. Biological evaluation of these derivatives demonstrated a good correlation between their cytotoxicity and their capacity to inhibit conversion of ceramide into sphingomyelin in melanoma cells. A series of potent and selective inhibitors of sphingomyelin production was thus identified. Furthermore, the good overall potency of an ω-aminated analogue allowed us to dissociate of the pharmacological action of jaspine B from its amphiphilic nature.

  尽管细胞毒性物质anhydrophytosphingosine jaspine B的全顺式四氢呋喃骨架被认为是相关药效基团，但对于这种两亲性分子中的脂肪链对其活性的影响却知之甚少。我们开发了一种合成策略，允许在jaspine的骨架中灵活引入各种亲脂性片段。这条路线通过两种不同的方法验证了jaspine B的合成。我们还制备了五个经过链修饰的类似物。这些衍生物的生物学评价显示，它们的细胞毒性与抑制黑色素瘤细胞中神经酰胺转化为鞘磷脂的能力之间存在良好的相关性。因此，我们鉴定出一组强效且选择性的鞘磷脂生产抑制剂。此外，一个ω-氨基化类似物表现出的良好整体效能，使我们能够将jaspine B的药理作用与其两亲性本质分离。