(2S,3S)-3-benzyl-1-<(1,1-dimethylethoxy)carbonyl>-2-<<(1,1-dimethylethyl)dimethylsilyloxy>methyl>-5-pyrrolidone | 126587-43-7

• 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: (2S,3S)-3-benzyl-1-<(1,1-dimethylethoxy)carbonyl>-2-<<(1,1-dimethylethyl)dimethylsilyloxy>methyl>-5-pyrrolidone
• 英文别名: tert-butyl (2S,3S)-3-benzyl-2-[[tert-butyl(dimethyl)silyl]oxymethyl]-5-oxopyrrolidine-1-carboxylate
• CAS: 126587-43-7
• 化学式: C₂₃H₃₇NO₄Si
• 分子量: 419.637
• InChiKey: NXLSUKWIHJOGOR-RBUKOAKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 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：

  (2S,3S)-3-benzyl-1-<(1,1-dimethylethoxy)carbonyl>-2-<<(1,1-dimethylethyl)dimethylsilyloxy>methyl>-5-pyrrolidone 在 盐酸 、 lithium aluminium tetrahydride 、 jones reagent 、 硫酸 、 potassium carbonate 、 丙酮 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 (2S,3S)-3-Benzyl-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 2-tert-butyl ester
  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：

  苄基苯基硫醚 在 正丁基锂 、 Raney nickel(W-2) 作用下， 以 水 、 丙酮 为溶剂， 生成 (2S,3S)-3-benzyl-1-<(1,1-dimethylethoxy)carbonyl>-2-<<(1,1-dimethylethyl)dimethylsilyloxy>methyl>-5-pyrrolidone
  参考文献：
  名称：

  类胡萝卜素的无环类似物的合成和神经兴奋活性

  摘要：

  合成了4-苄基谷氨酸的四种构型异构体，即类胡萝卜素的无环类似物，以检验它们的构效关系。

  DOI：

  10.1016/s0040-4039(01)80659-6

文献信息

• Acyclic analogs of kainoids: Their syntheses and depolarizing activities
  作者：Miwa Hashimoto (nee Yanagida)、Kimiko Hashimoto、Haruhisa Shirahama

  DOI：10.1016/0040-4020(95)01058-0

  日期：1996.2

  (4R)-4-amino-2-penten-5-olide and to protected (2S)- and (2R)-3-dehydro-2-hydroxymethyl-5-pyrrolidone. The β-methallyl- and β-isobutylglutamic acids were also synthesized in a similar manner. The depolarizing activities of these synthesized compounds were observed.

  β-苄基谷氨酸的四种立体异构体是通过将苄基苯硫醚迈克尔加成到受保护的（4 S）-和（4 R）-4-氨基-2-戊烯5-内酰胺以及受保护的（2 S）-和（ 2 R）-3-脱氢-2-羟甲基-5-吡咯烷酮。β-甲基烯丙基-和β-异丁基谷氨酸也以类似方式合成。观察到这些合成化合物的去极化活性。
• Syntheses of acyclic analogues of kainoids and neuroexcitatory activity
  作者：Miwa Yanagida、Kimiko Hashimoto、Michiko Ishida、Haruhiko Shinozaki、Haruhisa Shirahama

  DOI：10.1016/s0040-4039(01)80659-6

  日期：1989.1

  Four configurational isomers of 3-benzylglutamic acid, acyclic analogues of kainoids were synthesized to examine their structure-activity relationship.

  合成了4-苄基谷氨酸的四种构型异构体，即类胡萝卜素的无环类似物，以检验它们的构效关系。
• Inhibitors of hepatitis C virus NS3·4A protease. Part 3: P2 proline variants
  作者：Robert B Perni、Luc J Farmer、Kevin M Cottrell、John J Court、Lawrence F Courtney、David D Deininger、Cynthia A Gates、Scott L Harbeson、Joseph L Kim、Chao Lin、Kai Lin、Yu-Ping Luong、John P Maxwell、Mark A Murcko、Janos Pitlik、B.Govinda Rao、Wayne C Schairer、Roger D Tung、John H Van Drie、Keith Wilson、John A Thomson

  DOI：10.1016/j.bmcl.2004.01.078

  日期：2004.4

  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.