N-[(3aS,6R,6aS)-6-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-N-[(3S)-6-phenylmethoxy-2,3-dihydro-1-benzofuran-3-yl]hydroxylamine | 182823-42-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: N-[(3aS,6R,6aS)-6-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-N-[(3S)-6-phenylmethoxy-2,3-dihydro-1-benzofuran-3-yl]hydroxylamine
• CAS: 182823-42-3
• 化学式: C₂₇H₃₃NO₈
• 分子量: 499.561
• InChiKey: GQFKXSBXBWVJDD-ZPPWMSORSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  88.1
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  potassium cyanate 、 N-[(3aS,6R,6aS)-6-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-N-[(3S)-6-phenylmethoxy-2,3-dihydro-1-benzofuran-3-yl]hydroxylamine 以 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以87.3%的产率得到苯甲醇,-α--甲基-4-(2-甲基丙基)-,乙酸酯(9CI)
  参考文献：
  名称：

  Enantioselective Synthesis of 5-LO Inhibitor Hydroxyureas. Tandem Nucleophilic Addition−Intramolecular Cyclization of Chiral Nitrones

  摘要：

  An enantioselective synthesis of chiral hydroxyurea based 5-lipoxygenase inhibitors is reported via a five-step sequence in about 39% overall yield. The synthesis is based on a novel tandem nucleophilic addition-intramolecular cyclization reaction in which a chiral nitrone functions as the electrophilic acceptor species. A mannose-based chiral auxiliary controls the diastereoselectivity of the reaction in an 8:1 ratio. After the auxiliary removal and appropriate functionalization, a single recrystallization afforded the target structures in > 99% ee.

  DOI：

  10.1021/jo9621736
• 作为产物：
  描述：

  4-苯甲氧基-2-羟基苯甲醛 在 三正丁胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 6.0h， 生成 N-[(3aS,6R,6aS)-6-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-N-[(3S)-6-phenylmethoxy-2,3-dihydro-1-benzofuran-3-yl]hydroxylamine
  参考文献：
  名称：

  对映体选择性合成抑制5-LO的羟基脲。串联亲核加成和分子内环化法构建二氢-苯并呋喃核

  摘要：

  基于将二甲基亚砜基叶立德亲核加成到带有甘露糖衍生的手性助剂的腈上，描述了对5-LO抑制性手性羟基脲的对映选择性合成。然后通过初始加合物的自发环化来构建二氢苯并呋喃骨架，从而完成串联亲核加成-环化方案。

  DOI：

  10.1016/0040-4039(96)00922-7

文献信息

• Enantioselective Synthesis of 5-LO Inhibitor Hydroxyureas. Tandem Nucleophilic Addition−Intramolecular Cyclization of Chiral Nitrones
  作者：Ivan Lantos、Joseph Flisak、Li Liu、Richard Matsuoka、Wilf Mendelson、David Stevenson、Ken Tubman、Lynn Tucker、Wei-Yuan Zhang、Jerry Adams、Margaret Sorenson、Ravi Garigipati、Karl Erhardt、Steve Ross

  DOI：10.1021/jo9621736

  日期：1997.8.1

  An enantioselective synthesis of chiral hydroxyurea based 5-lipoxygenase inhibitors is reported via a five-step sequence in about 39% overall yield. The synthesis is based on a novel tandem nucleophilic addition-intramolecular cyclization reaction in which a chiral nitrone functions as the electrophilic acceptor species. A mannose-based chiral auxiliary controls the diastereoselectivity of the reaction in an 8:1 ratio. After the auxiliary removal and appropriate functionalization, a single recrystallization afforded the target structures in > 99% ee.
• Enantioselective synthesis of a 5-LO inhibiting hydroxyurea. Construction of the dihydro-benzofuran nucleus by tandem nucleophilic addition and intramolecular cyclization
  作者：Joseph R. Flisak、Ivan Lantos、Li Liu、Richard T. Matsuoka、Wilford L. Mendelson、Lynn M. Tucker、Anthony J. Villani、Wei-Yuan Zhang

  DOI：10.1016/0040-4039(96)00922-7

  日期：1996.7

  synthesis of a 5-LO inhibiting chiral hydroxyurea is described based on the nucleophilic addition of dimethylsulfoxonium ylide to a nitrone bearing a mannose-derived chiral auxiliary. The dihydrobenzofuran skeleton is then constructed by a spontaneous cyclization of the initial adduct, thus completing a tandem nucleophilic addition-cyclization protocol.

  基于将二甲基亚砜基叶立德亲核加成到带有甘露糖衍生的手性助剂的腈上，描述了对5-LO抑制性手性羟基脲的对映选择性合成。然后通过初始加合物的自发环化来构建二氢苯并呋喃骨架，从而完成串联亲核加成-环化方案。