(1R,2S,3S,6R,7R)-8-benzyloxycarbonyl-2-bromo-4-oxa-8-azatricyclo[4.3.1.0^3,7]decan-5-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1R,2S,3S,6R,7R)-8-benzyloxycarbonyl-2-bromo-4-oxa-8-azatricyclo[4.3.1.0^3,7]decan-5-one
• 英文别名: (1R,2S,3S,6S,7R)-8-benzyloxycarbonyl-2-bromo-4-oxa-8-azatricyclo[4.3.1.0(3,7)]decan-5-one；benzyl (1R,2S,3S,6S,7R)-2-bromo-5-oxo-4-oxa-8-azatricyclo[4.3.1.03,7]decane-8-carboxylate
• 化学式: C₁₆H₁₆BrNO₄
• 分子量: 366.211
• InChiKey: SPDLJDVZSPCVJQ-MBJXGIAVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1R,2S,3S,6R,7R)-8-benzyloxycarbonyl-2-bromo-4-oxa-8-azatricyclo[4.3.1.0^3,7]decan-5-one 在 N-甲基吗啉 、 水 、 氯甲酸乙酯 、 sodium hydroxide 、 锌 作用下， 以 甲醇 、 溶剂黄146 、 乙酸乙酯 、 丙酮 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Discovery of aminopiperidine-based Smac mimetics as IAP antagonists

  摘要：

  A series of structurally unique Smac mimetics that act as antagonists of inhibitor of apoptosis proteins (IAPs) has been discovered. While most previously described Smac mimetics contain the proline ring (or a similar cyclic motif) found in Smac, a key feature of the compounds described herein is that this ring has been removed. Despite this, compounds in this series potently bind to cIAP1 and elicit the expected phenotype of cIAP1 inhibition in cancer cells. Marked selectivity for cIAP1 over XIAP is observed for these compounds, which is attributed to a slight difference in the binding groove between the two proteins and the resulting steric interactions with the inhibitors. XIAP binding can be improved by constraining the inhibitor so that these unfavorable steric interactions are minimized. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.109
• 作为产物：
  描述：

  N-benzyloxycarbonyl-1,2-dihydropyridine 、 丙烯醛 在 sodium chlorite 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 溴 、 碳酸氢钠 作用下， 以 水 、 乙腈 、 叔丁醇 、 二氯甲烷 为溶剂， 反应 14.0h， 生成 (1R,2S,3S,6R,7R)-8-benzyloxycarbonyl-2-bromo-4-oxa-8-azatricyclo[4.3.1.0^3,7]decan-5-one
  参考文献：
  名称：

  （-）-奥司他韦的实用合成。

  摘要：

  DOI：

  10.1002/anie.200701754

文献信息

• A practical synthesis of (−)-oseltamivir
  作者：Nobuhiro Satoh、Takahiro Akiba、Satoshi Yokoshima、Tohru Fukuyama

  DOI：10.1016/j.tet.2008.09.103

  日期：2009.4

  is a potent inhibitor of neuraminidase, and is used worldwide as a drug for type A or B influenza. The industrial synthesis of oseltamivir uses shikimic acid as a starting material, but the price fluctuates, depending on the supply of star anise. We have developed a practical synthesis of oseltamivir from pyridine, which features an asymmetric Diels–Alder reaction of dihydropyridine using MacMillan's

  磷酸奥塞米韦（达菲®）是神经氨酸酶的有效抑制剂，并且在世界范围内使用，作为A型或B型流感的药物。奥司他韦的工业合成使用sh草酸作为起始原料，但价格随八角茴香的供应而波动。我们已经开发了从吡啶中合成奥司他韦的实用方法，该方法具有使用MacMillan催化剂的二氢吡啶的不对称Diels-Alder反应，溴内酯化，用PhI（OAc）2进行的霍夫曼重排和双环[2.2.2]系统的多米诺变换形成氮丙啶化合物。
• Discovery of aminopiperidine-based Smac mimetics as IAP antagonists
  作者：Edward J. Hennessy、Jamal C. Saeh、Li Sha、Terry MacIntyre、Haiyun Wang、Nicholas A. Larsen、Brian M. Aquila、Andrew D. Ferguson、Naomi M. Laing、Charles A. Omer

  DOI：10.1016/j.bmcl.2011.12.109

  日期：2012.2

  A series of structurally unique Smac mimetics that act as antagonists of inhibitor of apoptosis proteins (IAPs) has been discovered. While most previously described Smac mimetics contain the proline ring (or a similar cyclic motif) found in Smac, a key feature of the compounds described herein is that this ring has been removed. Despite this, compounds in this series potently bind to cIAP1 and elicit the expected phenotype of cIAP1 inhibition in cancer cells. Marked selectivity for cIAP1 over XIAP is observed for these compounds, which is attributed to a slight difference in the binding groove between the two proteins and the resulting steric interactions with the inhibitors. XIAP binding can be improved by constraining the inhibitor so that these unfavorable steric interactions are minimized. (C) 2011 Elsevier Ltd. All rights reserved.
• A Practical Synthesis of (−)-Oseltamivir
  作者：Nobuhiro Satoh、Takahiro Akiba、Satoshi Yokoshima、Tohru Fukuyama

  DOI：10.1002/anie.200701754

  日期：2007.7.23