methyl 1N-tert-butoxycarbonyl-4-exomethylene-pyrrolidine-(2R)-carboxylate | 256488-01-4

• 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: methyl 1N-tert-butoxycarbonyl-4-exomethylene-pyrrolidine-(2R)-carboxylate
• 英文别名: 1-(tert-butyl) 2-methyl (R)-4-methylenepyrrolidine-1,2-dicarboxylate；2-methyl 1-tert-butyl (2R)-4-methylenepyrrolidine-1,2-dicarboxylate；(R)-1-Tert-butyl 2-methyl 4-methylenepyrrolidine-1,2-dicarboxylate；1-O-tert-butyl 2-O-methyl (2R)-4-methylidenepyrrolidine-1,2-dicarboxylate
• CAS: 256488-01-4
• 化学式: C₁₂H₁₉NO₄
• 分子量: 241.287
• InChiKey: CEEDNDKFZGTXOZ-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 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：

  methyl 1N-tert-butoxycarbonyl-4-exomethylene-pyrrolidine-(2R)-carboxylate 在 羟胺 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 19.0h， 生成 (R)-4-Methylene-1-(4-phenoxy-benzenesulfonyl)-pyrrolidine-2-carboxylic acid hydroxyamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Matrix Metalloproteinase Inhibitors Derived from a Modified Proline Scaffold

  摘要：

  The synthesis and structure-activity relationship (SAR) studies of a series of proline-based matrix metalloproteinase inhibitors are described. The data reveal a remarkable potency enhancement in those compounds that contain an sp(2) center at the C-4 carbon of the ring relative to similar, saturated compounds. This effect was noted in compounds that contained a functionalized oxime moiety or an exomethylene at C-4, and the potencies were typically <10 nM for MMP-3 and <100 nM for MMP-1. Comparisons were then made against compounds with similar functionality where the C-4 carbon was reduced to sp(3) hybridization and the effect was typically an order of magnitude loss in potency. A comparison of compounds 14 and 34 exemplifies this observation. An X-ray structure was obtained for a stromelysin-inhibitor complex which provided insights into the SAR and selectivity trends observed within the series. In vitro intestinal permeability data for many compounds was also accumulated.

  DOI：

  10.1021/jm9904699
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 ruthenium trichloride 、 sodium periodate 、 三乙胺 作用下， 生成 N-BOC-4-亚甲基-L-脯氨酸甲酯 、 methyl 1N-tert-butoxycarbonyl-4-exomethylene-pyrrolidine-(2R)-carboxylate
  参考文献：
  名称：

  新型Boc保护的环丙烷修饰的脯氨酸类似物的合成

  摘要：

  据报道，Boc保护的5-azaspiro [2.4]庚烷-6-羧酸的新成员是环丙烷修饰的脯氨酸文库的一个新成员的Boc衍生物的合成。从（2 S，4 R）-4-羟基脯氨酸开始，使用改良的Simmons-Smith反应作为关键步骤，分六步进行了合成。仔细选择所有步骤的反应条件，以避免中间体和最终产物在手性中心发生外消旋化。

  DOI：

  10.1016/j.tetlet.2012.05.020

文献信息

• [EN] CONJUGATES FOR TREATING DISEASES<br/>[FR] CONJUGUÉS POUR LE TRAITEMENT DE MALADIES
  申请人：ENDOCYTE INC

  公开号：WO2016148674A1

  公开（公告）日：2016-09-22

  The present disclosure relates to pyrrolobenzodiazepine (PBD) prodrugs and conjugates thereof. The present disclosure also relates to pharmaceutical compositions of the conjugates described herein, methods of making and methods of using the same.

  本公开涉及吡咯苯并二氮杂环（PBD）前药及其结合物。本公开还涉及所述结合物的药物组合物，制备方法和使用方法。
• Ni-Catalyzed Arylboration of Unactivated Alkenes: Scope and Mechanistic Studies
  作者：Stephen R. Sardini、Alison L. Lambright、Grace L. Trammel、Humair M. Omer、Peng Liu、M. Kevin Brown

  DOI：10.1021/jacs.9b03991

  日期：2019.6.12

  unactivated monosubstituted, 1,1-disubstituted, and trisubstituted alkenes is disclosed. The reaction is notable in that it converts highly substituted alkenes, aryl bromides, and diboron reagents to products that contain a quaternary carbon and a synthetically versatile carbon-boron bond with control of stereoselectivity and regioselectivity. In addition, the method is demonstrated to be useful for the

  公开了一种未活化的单取代、1,1-二取代和三取代烯烃的Ni催化芳基硼化反应的方法。该反应的值得注意之处在于，它将高度取代的烯烃、芳基溴和二硼试剂转化为含有季碳和合成通用碳硼键的产物，并控制立体选择性和区域选择性。此外，该方法被证明可用于合成饱和氮杂环，这是药物化合物中的重要基序。最后，由于所表现出的不寻常的反应性，我们通过计算和实验技术研究了反应的机理细节。
• Synthesis of a novel Boc-protected cyclopropane-modified proline analogue
  作者：Andriy V. Tymtsunik、Vitaliy A. Bilenko、Yevhen M. Ivon、Oleksandr O. Grygorenko、Igor V. Komarov

  DOI：10.1016/j.tetlet.2012.05.020

  日期：2012.7

  The synthesis of the Boc derivative of a novel member of the cyclopropane-modified proline library, Boc-protected 5-azaspiro[2.4]heptane-6-carboxylic acid, is reported. The synthesis was performed in six steps starting from (2S,4R)-4-hydroxyproline using a modified Simmons–Smith reaction as the key step. The reaction conditions for all the steps were carefully selected to avoid racemization at the

  据报道，Boc保护的5-azaspiro [2.4]庚烷-6-羧酸的新成员是环丙烷修饰的脯氨酸文库的一个新成员的Boc衍生物的合成。从（2 S，4 R）-4-羟基脯氨酸开始，使用改良的Simmons-Smith反应作为关键步骤，分六步进行了合成。仔细选择所有步骤的反应条件，以避免中间体和最终产物在手性中心发生外消旋化。
• Design, Synthesis, and Biological Evaluation of Matrix Metalloproteinase Inhibitors Derived from a Modified Proline Scaffold
  作者：Menyan Cheng、Biswanath De、Neil G. Almstead、Stanislaw Pikul、Martin E. Dowty、Charles R. Dietsch、C. Michelle Dunaway、Fei Gu、Lily C. Hsieh、Michael J. Janusz、Yetunde O. Taiwo、Michael G. Natchus、Tomas Hudlicky、Martin Mandel

  DOI：10.1021/jm9904699

  日期：1999.12.1

  The synthesis and structure-activity relationship (SAR) studies of a series of proline-based matrix metalloproteinase inhibitors are described. The data reveal a remarkable potency enhancement in those compounds that contain an sp(2) center at the C-4 carbon of the ring relative to similar, saturated compounds. This effect was noted in compounds that contained a functionalized oxime moiety or an exomethylene at C-4, and the potencies were typically <10 nM for MMP-3 and <100 nM for MMP-1. Comparisons were then made against compounds with similar functionality where the C-4 carbon was reduced to sp(3) hybridization and the effect was typically an order of magnitude loss in potency. A comparison of compounds 14 and 34 exemplifies this observation. An X-ray structure was obtained for a stromelysin-inhibitor complex which provided insights into the SAR and selectivity trends observed within the series. In vitro intestinal permeability data for many compounds was also accumulated.