(R)-alpha-氨基苯丁酸叔丁酯 | 740055-30-5

• 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
• 中文名称: (R)-alpha-氨基苯丁酸叔丁酯
• 中文别名: D-高苯丙氨酸叔丁酯
• 英文名称: D-homophenylalanine tert-butyl ester
• 英文别名: D-HoPhe-OtBu；(R)-tert-butyl 2-amino-4-phenylbutanoate；D-Homophenylalanine tert-Butyl Ester；tert-butyl (2R)-2-amino-4-phenylbutanoate
• CAS: 740055-30-5
• 化学式: C₁₄H₂₁NO₂
• 分子量: 235.326
• InChiKey: CANQRTXTMVVNCH-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-alpha-氨基苯丁酸叔丁酯 在 盐酸 、 水 、 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-2-(N-isopentylnaphthalene-2-sulfonamido)-4-phenylbutanoic acid
  参考文献：
  名称：

  Potent and selective 2-naphthylsulfonamide substituted hydroxamic acid inhibitors of matrix metalloproteinase-13

  摘要：

  The matrix metalloproteinase enzyme MMP-13 plays a key role in the degradation of type II collagen in cartilage and bone in osteoarthritis (OA). An effective MMP-13 inhibitor would provide a disease modifying therapy for the treatment of arthritis, although this goal still continues to elude the pharmaceutical industry due to issues with safety. Our efforts have resulted in the discovery of a series of hydroxamic acid inhibitors of MMP-13 that do not significantly inhibit MMP-2 (gelatinase-1). MMP-2 has been implicated in the musculoskeletal side effects resulting from pan-MMP inhibition due to findings from spontaneously occurring human MMP-2 deletions. Analysis of the SAR of hundreds of previously prepared hydroxamate based MMP inhibitors lead us to 2-naphthylsulfonamide substituted hydroxamates which exhibited modest selectivity for MMP-13 versus MMP-2. This Letter describes the lead optimization of 1 and identification of inhibitors exhibiting >100-fold selectivity for MMP-13 over MMP-2 (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.087
• 作为产物：
  描述：

  tert-butyl 2-oxo-4-phenylbutanoate 在 N-[4-[(R)-[(2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-[3-(2,4,6-trimethylphenyl)propoxy]methyl]quinolin-6-yl]-2,4,6-triethylbenzenesulfonamide 、 邻氯苯甲胺 、 盐酸 作用下， 以 苯 、 四氢呋喃 为溶剂， 反应 60.0h， 以87%的产率得到(R)-alpha-氨基苯丁酸叔丁酯
  参考文献：
  名称：

  从α-酮酯到手性α-氨基酯的高效不对称仿生转氨

  摘要：

  描述了一种有效的不对称仿生氨基转移的α-酮酯与奎宁衍生物作为手性碱。可以以高收率和对映选择性合成多种含有各种官能团的α-氨基酯。

  DOI：

  10.1021/ol302427d

文献信息

• Discovery and Structure–Activity Relationships of the Neoseptins: A New Class of Toll-like Receptor-4 (TLR4) Agonists
  作者：Matthew D. Morin、Ying Wang、Brian T. Jones、Lijing Su、Murali M. R. P. Surakattula、Michael Berger、Hua Huang、Elliot K. Beutler、Hong Zhang、Bruce Beutler、Dale L. Boger

  DOI：10.1021/acs.jmedchem.6b00177

  日期：2016.5.26

  Herein, we report studies leading to the discovery of the neoseptins and a comprehensive examination of the structure–activity relationships (SARs) of this new class of small-molecule mouse Toll-like receptor 4 (mTLR4) agonists. The compounds in this class, which emerged from screening an α-helix mimetic library, stimulate the immune response, act by a well-defined mechanism (mouse TLR4 agonist), are

  在本文中，我们报道了导致新肽段的发现以及对这种新型小分子小鼠Toll样受体4（mTLR4）激动剂的结构-活性关系（SAR）的全面研究的报告。该类化合物是通过筛选α-螺旋模拟物文库而产生的，可刺激免疫反应，并通过明确的机制发挥作用（小鼠TLR4激动剂），易于生产和结构操纵，具有精美的SAR，无毒，与脂多糖相比，即使它们共享相同的受体，也能引起改善的和质上不同的反应。
• Organocatalytic Asymmetric Biomimetic Transamination: From α-Keto Esters to Optically Active α-Amino Acid Derivatives
  作者：Xiao Xiao、Ying Xie、Cunxiang Su、Mao Liu、Yian Shi

  DOI：10.1021/ja203138q

  日期：2011.8.24

  This paper describes an effective chiral base-catalyzed biomimetic transamination of α-keto esters using simple benzyl amines. A wide variety of α-amino esters containing various functional groups can be synthesized in high enantioselectivity and reasonable yield.

  本文描述了使用简单的苄胺对 α-酮酯进行有效的手性碱催化仿生氨基转移。可以以高对映选择性和合理的收率合成多种含有各种官能团的α-氨基酯。
• Asymmetric Synthesis of α-Amino Acids by Organocatalytic Biomimetic Transamination
  作者：Qi-Kai Kang、Sermadurai Selvakumar、Keiji Maruoka

  DOI：10.1021/acs.orglett.9b00588

  日期：2019.4.5

  A biomimetic enantioselective transamination of α-keto ester derivatives can be realized under mild conditions by using chiral quaternary ammonium arenecarboxylates in the absence of base additives. The corresponding α-amino acids can be used as versatile intermediates for further synthetic transformations that furnish chiral pyrrolidine and octahydroindolizine derivatives.

  α-酮酯衍生物的仿生对映体选择性氨基转移可以在温和的条件下，通过在不存在碱添加剂的情况下使用手性季铵芳烃羧酸酯来实现。相应的α-氨基酸可用作用于进一步的合成转化的通用中间体，其提供手性吡咯烷和八氢吲哚嗪衍生物。
• The effect of benzyl amine on the efficiency of the base-catalyzed transamination of α-keto esters
  作者：Fazhen Xue、Xiao Xiao、Haining Wang、Yian Shi

  DOI：10.1016/j.tet.2012.06.023

  日期：2012.8

  This paper describes the effect of benzyl amine on the base-catalyzed transamination of alpha-keto esters. Among various benzyl amines examined, o-HOC6H4CH2NH2 was found to be highly effective for the reaction, affording a wide variety of alpha-amino esters in good yields. The o-OH group of the benzyl amine facilitates the transamination process likely via H-bond. Moderate enantiomeric excess was obtained for alpha-amino ester when a quinine derived catalyst was used. (C) 2012 Elsevier Ltd. All rights reserved.
• Potent and selective 2-naphthylsulfonamide substituted hydroxamic acid inhibitors of matrix metalloproteinase-13
  作者：Ruben A. Tommasi、Sven Weiler、Leslie W. McQuire、Olivier Rogel、Mark Chambers、Kirk Clark、John Doughty、James Fang、Vishwas Ganu、Jonathan Grob、Ronald Goldberg、Robert Goldstein、Stacey LaVoie、Raviraj Kulathila、William Macchia、Richard Melton、Clayton Springer、Marc Walker、Jing Zhang、Lijuan Zhu、Michael Shultz

  DOI：10.1016/j.bmcl.2011.08.087

  日期：2011.11

  The matrix metalloproteinase enzyme MMP-13 plays a key role in the degradation of type II collagen in cartilage and bone in osteoarthritis (OA). An effective MMP-13 inhibitor would provide a disease modifying therapy for the treatment of arthritis, although this goal still continues to elude the pharmaceutical industry due to issues with safety. Our efforts have resulted in the discovery of a series of hydroxamic acid inhibitors of MMP-13 that do not significantly inhibit MMP-2 (gelatinase-1). MMP-2 has been implicated in the musculoskeletal side effects resulting from pan-MMP inhibition due to findings from spontaneously occurring human MMP-2 deletions. Analysis of the SAR of hundreds of previously prepared hydroxamate based MMP inhibitors lead us to 2-naphthylsulfonamide substituted hydroxamates which exhibited modest selectivity for MMP-13 versus MMP-2. This Letter describes the lead optimization of 1 and identification of inhibitors exhibiting >100-fold selectivity for MMP-13 over MMP-2 (C) 2011 Elsevier Ltd. All rights reserved.