1-benzyl 2-methyl 2-(3'-hydroxypropyl)pyrrolidine-1,2-dicarboxylate | 161417-44-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1-benzyl 2-methyl 2-(3'-hydroxypropyl)pyrrolidine-1,2-dicarboxylate
• 英文别名: 1-Benzyloxycarbonyl-2-(3-hydroxypropyl)-2-(methoxycarbonyl) pyrrolidine；Methyl 1-Cbz-2-(3-hydroxypropyl)pyrrolidine-2-carboxylate；1-O-benzyl 2-O-methyl 2-(3-hydroxypropyl)pyrrolidine-1,2-dicarboxylate
• CAS: 161417-44-3
• 化学式: C₁₇H₂₃NO₅
• 分子量: 321.373
• InChiKey: SJKJUPFXBZEWHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-benzyl 2-methyl 2-(3'-hydroxypropyl)pyrrolidine-1,2-dicarboxylate 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以66%的产率得到1-benzyl 2-methyl 2-(2-formylethyl)pyrrolidine-1,2-dicarboxylate
  参考文献：
  名称：

  Synthesis and evaluation of C8-substituted 4.5-spiro lactams as Glycogen Phosphorylase a inhibitors

  摘要：

  An effective synthesis of 4.5-spiro lactams 28/29, has been completed in nine steps with an overall yield of 5.8%. The 4.5-spiro lactams were made from 2-allyl-Cbz-Pro-OMe 21, which was converted into the corresponding alcohol 22 via a hindered borane reaction with (2-methylbutyl)(2)borane. Subsequent Swern oxidation of 22 gave novel aldehyde 23. Aldehyde 23 was treated under Bucherer-Bergs reaction conditions to give hydantoin 26, which was opened to the corresponding amino acid 30 using di-tert-butyl dicarbonate and DMAP followed by hydrolysis. Treatment of amino acid 30 with acidic methanol gave 4.5-spiro lactams 28/29. Only 4.5-spiro lactam 29 displayed moderate activity against GPa with an IC50 of 241 mu M. (c) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2012.12.004
• 作为产物：
  描述：

  2-甲基吡咯烷-1,2-二羧酸-1-苄酯 在 硼烷四氢呋喃络合物 、 双氧水 、 2-甲基-丁烯 、 sodium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 生成 1-benzyl 2-methyl 2-(3'-hydroxypropyl)pyrrolidine-1,2-dicarboxylate
  参考文献：
  名称：

  Synthesis and evaluation of C8-substituted 4.5-spiro lactams as Glycogen Phosphorylase a inhibitors

  摘要：

  An effective synthesis of 4.5-spiro lactams 28/29, has been completed in nine steps with an overall yield of 5.8%. The 4.5-spiro lactams were made from 2-allyl-Cbz-Pro-OMe 21, which was converted into the corresponding alcohol 22 via a hindered borane reaction with (2-methylbutyl)(2)borane. Subsequent Swern oxidation of 22 gave novel aldehyde 23. Aldehyde 23 was treated under Bucherer-Bergs reaction conditions to give hydantoin 26, which was opened to the corresponding amino acid 30 using di-tert-butyl dicarbonate and DMAP followed by hydrolysis. Treatment of amino acid 30 with acidic methanol gave 4.5-spiro lactams 28/29. Only 4.5-spiro lactam 29 displayed moderate activity against GPa with an IC50 of 241 mu M. (c) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2012.12.004

文献信息

• Enantioselective Total Synthesis of Avrainvillamide and the Stephacidins
  作者：Phil S. Baran、Benjamin D. Hafensteiner、Narendra B. Ambhaikar、Carlos A. Guerrero、John D. Gallagher

  DOI：10.1021/ja061660s

  日期：2006.7.1

  complete stereocontrol. The information gained in these model studies enabled an enantioselective total synthesis of stephacidin A. The absolute configuration of these alkaloids was firmly established in collaboration with Professor William Fenical. A full account of our successful efforts to convert stephacidin A into stephacidin B via avrainvillamide is presented. Finally, the first analogues of these natural

  在本文中，提供了有关我们全合成 avrainvillamide 和 stepphacidins 的完整详细信息。在介绍和总结这一结构复杂的抗癌天然产物家族的先前合成研究之后，描述了最终合成方法的演变。因此，为构建这些生物碱共有的特征双环[2.2.2]二氮杂辛烷环系统，提供了三个独立模型研究的详尽描述。第一种和第二种方法试图分别使用正式的 Diels-Alder 和乙烯基自由基途径来构建核心。尽管这些策略未能实现其主要目标，但它们促进了一种新的、机械上有趣的方法的开发，用于合成吲哚烯酰胺，例如在许多生物活性天然产物中发现的那些。描述了这种用于色氨酸衍生物直接脱氢的简单方法的范围和通用性。最后，描述了通往这些生物碱核心的第三条成功途径的细节，其特征是氧化 CC 键的形成。具体而言，两种不同类型的羰基物质（酯和酰胺）的第一次杂偶联以良好的收率、制备规模和完全立体控制完成。在这些模型研究中获得的信息使
• HETEROCYCLIC ETHER COMPOUNDS THAT ENHANCE COGNITIVE FUNCTION
  申请人：ABBOTT LABORATORIES

  公开号：EP0663912B1

  公开（公告）日：2001-12-12
• 7a-HETEROCYCLE-SUBSTITUTED HEXAHYDRO-1H-PYRROLIZINE COMPOUNDS USEFUL IN CONTROLLING CHEMICAL SYNAPTIC TRANSMISSION
  申请人：Abbott Laboratories

  公开号：EP0970083B1

  公开（公告）日：2003-04-16
• US5733912A
  申请人：——

  公开号：US5733912A

  公开（公告）日：1998-03-31
• Synthesis and evaluation of C8-substituted 4.5-spiro lactams as Glycogen Phosphorylase a inhibitors
  作者：Wendy A. Loughlin、Stephanie S. Schweiker、Ian D. Jenkins、Luke C. Henderson

  DOI：10.1016/j.tet.2012.12.004

  日期：2013.2

  An effective synthesis of 4.5-spiro lactams 28/29, has been completed in nine steps with an overall yield of 5.8%. The 4.5-spiro lactams were made from 2-allyl-Cbz-Pro-OMe 21, which was converted into the corresponding alcohol 22 via a hindered borane reaction with (2-methylbutyl)(2)borane. Subsequent Swern oxidation of 22 gave novel aldehyde 23. Aldehyde 23 was treated under Bucherer-Bergs reaction conditions to give hydantoin 26, which was opened to the corresponding amino acid 30 using di-tert-butyl dicarbonate and DMAP followed by hydrolysis. Treatment of amino acid 30 with acidic methanol gave 4.5-spiro lactams 28/29. Only 4.5-spiro lactam 29 displayed moderate activity against GPa with an IC50 of 241 mu M. (c) 2012 Published by Elsevier Ltd.