(S)-1-(1-butyl)-5-oxo-3-pyrrolidinecarboxylic acid | 755025-26-4

• 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: (S)-1-(1-butyl)-5-oxo-3-pyrrolidinecarboxylic acid
• 英文别名: (3S)-1-butyl-5-oxopyrrolidine-3-carboxylic acid
• CAS: 755025-26-4
• 化学式: C₉H₁₅NO₃
• 分子量: 185.223
• InChiKey: LLPSQGIRADJCIU-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl (R)-2-((1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxypropyl)-4-benzylpiperazine-1-carboxylate 、 (S)-1-(1-butyl)-5-oxo-3-pyrrolidinecarboxylic acid 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 生成 tert-butyl (R)-4-benzyl-2-((1S,2S)-2-((S)-1-butyl-5-oxopyrrolidine-3-carboxamido)-3-(3,5-difluorophenyl)-1-hydroxypropyl)piperazine-1-carboxylate
  参考文献：
  名称：

  Piperazine sulfonamide BACE1 inhibitors: Design, synthesis, and in vivo characterization

  摘要：

  With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2' sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral A beta(40) in transgenic mice with a single subcutaneous dose. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.03.050
• 作为产物：
  描述：

  衣康酸二甲酯 在 porcine pancreatic lipase 作用下， 以 甲醇 、 phosphate buffer 为溶剂， 反应 12.0h， 生成 (S)-1-(1-butyl)-5-oxo-3-pyrrolidinecarboxylic acid
  参考文献：
  名称：

  化学合成对映体纯的对羟基乙酸甲酯的氮杂类似物和甲基β-脯氨酸的两种对映体的化学酶法

  摘要：

  通过酶促拆分相应的手性外消旋混合物，获得1-烷基-5-氧代-3-吡咯烷羧酸的对映体纯甲酯。在1-苄基衍生物和α-胰凝乳蛋白酶之间观察到特别有利的相互作用，这也得到分子力学计算的支持，其对映体比率E超过200。内酰胺的绝对构型是通过CD光谱法确定的。从所得对映体纯的（99％ee）（S）-（+）-1-苄基-3-吡咯烷羧酸和（R）-（-）-1-苄基-3-吡咯烷甲酸甲酯，（+ ）和（-）-β-脯氨酸的合成产率分别为99％ee和18％和22％。

  DOI：

  10.1016/s0957-4166(01)00523-7

文献信息

• Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors
  作者：J.N. Cumming、T.X. Le、S. Babu、C. Carroll、X. Chen、L. Favreau、P. Gaspari、T. Guo、D.W. Hobbs、Y. Huang、U. Iserloh、M.E. Kennedy、R. Kuvelkar、G. Li、J. Lowrie、N.A. McHugh、L. Ozgur、J. Pan、E.M. Parker、K. Saionz、A.W. Stamford、C. Strickland、D. Tadesse、J. Voigt、L. Wang、Y. Wu、L. Zhang、Q. Zhang

  DOI：10.1016/j.bmcl.2008.04.050

  日期：2008.6

  Guided by structure-based design, we synthesized two novel series of potent inhibitors of BACE1 and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2' pocket.
• Piperazine sulfonamide BACE1 inhibitors: Design, synthesis, and in vivo characterization
  作者：Jared Cumming、Suresh Babu、Ying Huang、Carolyn Carrol、Xia Chen、Leonard Favreau、William Greenlee、Tao Guo、Matthew Kennedy、Reshma Kuvelkar、Thuy Le、Guoqing Li、Nansie McHugh、Peter Orth、Lynne Ozgur、Eric Parker、Kurt Saionz、Andrew Stamford、Corey Strickland、Dawit Tadesse、Johannes Voigt、Lili Zhang、Qi Zhang

  DOI：10.1016/j.bmcl.2010.03.050

  日期：2010.5

  With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2' sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral A beta(40) in transgenic mice with a single subcutaneous dose. (C) 2010 Elsevier Ltd. All rights reserved.
• A chemoenzymatic approach to the synthesis of enantiomerically pure aza analogues of paraconic acid methyl ester and both enantiomers of methyl β-proline
  作者：Fulvia Felluga、Giuliana Pitacco、Massimo Prodan、Sabrina Pricl、Marco Visintin、Ennio Valentin

  DOI：10.1016/s0957-4166(01)00523-7

  日期：2001.12

  Enantiopure methyl esters of 1-alkyl-5-oxo-3-pyrrolidinecarboxylic acids were obtained by enzymatic resolution of the corresponding chiral racemic mixtures. A particularly favourable interaction, also supported by molecular mechanics calculations, was observed between the 1-benzyl derivative and α-chymotrypsin, for which the enantiomeric ratio, E, exceeded 200. The absolute configurations of the lactams

  通过酶促拆分相应的手性外消旋混合物，获得1-烷基-5-氧代-3-吡咯烷羧酸的对映体纯甲酯。在1-苄基衍生物和α-胰凝乳蛋白酶之间观察到特别有利的相互作用，这也得到分子力学计算的支持，其对映体比率E超过200。内酰胺的绝对构型是通过CD光谱法确定的。从所得对映体纯的（99％ee）（S）-（+）-1-苄基-3-吡咯烷羧酸和（R）-（-）-1-苄基-3-吡咯烷甲酸甲酯，（+ ）和（-）-β-脯氨酸的合成产率分别为99％ee和18％和22％。