(4R,5S)-1-tert-butoxycarbonyl-4-tert-butyl-(5-tert-butyldimethylsilyloxymethyl)pyrrolidin-2-one | 410097-23-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (4R,5S)-1-tert-butoxycarbonyl-4-tert-butyl-(5-tert-butyldimethylsilyloxymethyl)pyrrolidin-2-one
• 英文别名: tert-butyl (2S,3R)-3-tert-butyl-2-[[tert-butyl(dimethyl)silyl]oxymethyl]-5-oxopyrrolidine-1-carboxylate
• CAS: 410097-23-3
• 化学式: C₂₀H₃₉NO₄Si
• 分子量: 385.619
• InChiKey: LNQVJGMKPCTFHV-LSDHHAIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.21
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 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：

  (4R,5S)-1-tert-butoxycarbonyl-4-tert-butyl-(5-tert-butyldimethylsilyloxymethyl)pyrrolidin-2-one 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 生成 (4R,5S)-4-tert-Butyl-5-hydroxymethyl-pyrrolidin-2-one
  参考文献：
  名称：

  Inhibitors of hepatitis C virus NS3·4A protease. Part 3: P2 proline variants

  摘要：

  We recently described the identification of an optimized alpha-ketoamide warhead for our series of HCV NS3(.)4A inhibitors. We report herein a series of HCV protease inhibitors incorporating 3-alkyl-substituted prolines in P-2. These compounds show exceptional enzymatic and cellular potency given their relatively small size. The marked enhancement of activity of these 3-substituted proline derivatives relative to previously reported 4-hydroxyproline derivatives constitutes additional evidence for the importance of the S-2 binding pocket as the defining pharmacophore for inhibition of the NS3(.)4A enzyme. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.01.078
• 作为产物：
  描述：

  bromozinc(1+),2-methylpropane 、 (2S,3R)-N-(叔-丁基氧羰基)-O-(叔-丁基)二甲基硅烷基-3,4-去氢-焦谷氨醇 在 三氟化硼乙醚 、 三甲基氯硅烷 作用下， 以 四氢呋喃 为溶剂， 以64%的产率得到(4R,5S)-1-tert-butoxycarbonyl-4-tert-butyl-(5-tert-butyldimethylsilyloxymethyl)pyrrolidin-2-one
  参考文献：
  名称：

  Inhibitors of hepatitis C virus NS3·4A protease. Part 3: P2 proline variants

  摘要：

  We recently described the identification of an optimized alpha-ketoamide warhead for our series of HCV NS3(.)4A inhibitors. We report herein a series of HCV protease inhibitors incorporating 3-alkyl-substituted prolines in P-2. These compounds show exceptional enzymatic and cellular potency given their relatively small size. The marked enhancement of activity of these 3-substituted proline derivatives relative to previously reported 4-hydroxyproline derivatives constitutes additional evidence for the importance of the S-2 binding pocket as the defining pharmacophore for inhibition of the NS3(.)4A enzyme. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.01.078

文献信息

• Mixed Cyano-Gilman Cuprates - Advances in Conjugate Addition to α,β-Unsaturated Pyroglutaminol
  作者：Ulf Madsen、Lennart Bunch、Povl Krogsgaard-Larsen

  DOI：10.1055/s-2002-19303

  日期：——

  Conjugate addition of lower order cuprates to protected α,β-unsaturated pyroglutaminol 1 is of limited value, mainly due to the requirement for a large excess of the transferable ligand (10 equiv). Here we report advances using mixed cyano-Gilman cuprates which allow the use of only 1.2 equiv of the transferable ligand, to give the desired product in acceptable to good yield (68-84%). Diethyl ether as the solvent was found advantageous versus THF, since the use of TMSCl could be avoided.

  低阶铜酸盐与受保护的δ,δ-不饱和焦谷氨醇 1 的共轭加成作用价值有限，这主要是由于需要大量过量的可转移配体（10 等量）。在此，我们报告了使用混合氰基-吉尔曼铜酸盐所取得的进展，只需使用 1.2 个等量的可转移配体，就能以可接受到良好的收率（68%-84%）得到所需的产物。二乙醚作为溶剂比四氢呋喃更有优势，因为可以避免使用 TMSCl。