(2R,3S,4S)-2-(benzylamino)-4-<<(1,1-dimethylethoxy)carbonyl>amino>-3-hydoxy-5-phenylpentanoic acid | 161510-68-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2R,3S,4S)-2-(benzylamino)-4-<<(1,1-dimethylethoxy)carbonyl>amino>-3-hydoxy-5-phenylpentanoic acid
• 英文别名: (2R,3R,4S)-2-(benzylamino)-4-(tert-butoxycarbonylamino)-3-hydroxy-5-phenylpentanoic acid；(2R,3R,4S)-2-(benzylamino)-3-hydroxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-phenylpentanoic acid
• CAS: 161510-68-5
• 化学式: C₂₃H₃₀N₂O₅
• 分子量: 414.502
• InChiKey: ZIRHTBFQVAJFAW-XUVXKRRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  108
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,3S,4S)-2-(benzylamino)-4-<<(1,1-dimethylethoxy)carbonyl>amino>-3-hydoxy-5-phenylpentanoic acid 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 (2R,3S,4S)-N-(4-amino-2-(benzylamino)-3-hydroxy-5-phenylpentanoyl)valine benzamide
  参考文献：
  名称：

  Inhibitors of HIV-1 Proteinase Containing 2-Heterosubstituted 4-Amino-3-hydroxy-5-phenylpentanoic Acid: Synthesis, Enzyme Inhibition, and Antiviral Activity

  摘要：

  A convenient procedure for the synthesis of 2-heterosubstituted statine derivatives as novel building blocks in HN-protease inhibitors has been developed. The synthesis starts with protected L-phenylalaninols, which were converted to gamma-amino alpha,beta-unsaturated esters in a one-pot procedure. A highly diastereoseletive epoxidation of the N-protected (E)-enoates, followed by regioselective ring opening of the corresponding 2,3-epoxy esters with a variety of heteronucleophiles, resulted in 2-heterosubstituted statine derivatives. The overall stereochemical outcome of the transformations meets the required configuration of HIV-protease inhibitors. The short, synthetically flexible, and highly diastereoselective synthesis of 2-heterosubstituted statines has enabled a broad derivation, covering the S3, S2, and S1'-S3' sites of the enzyme. In a series of 46 derivatives, several potent inhibitors were obtained with K-i values as low as 3.4 nM and antiviral activity in the lower nanomolar-range. The structural parameters of the compounds which determine the potency of inhibition and selectivity for the viral enzyme are discussed.

  DOI：

  10.1021/jm00045a013
• 作为产物：
  描述：

  N-Boc-L-苯丙氨醛 在 sodium hydroxide 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 203.0h， 生成 (2R,3S,4S)-2-(benzylamino)-4-<<(1,1-dimethylethoxy)carbonyl>amino>-3-hydoxy-5-phenylpentanoic acid
  参考文献：
  名称：

  设计和合成新型的基于呋喃的分子作为潜在的20S蛋白酶体抑制剂。

  摘要：

  已经设计和合成了一类新型的呋喃基化合物作为潜在的20S蛋白酶体抑制剂，其中九种化合物是肽衍生物，六种分子是他汀类肽模拟物。将C末端呋喃基部分作为基于呋喃的氨基酸引入靶分子。稳定地获得了所有化合物，产率中等至高。化合物12是选择性的中度有效的蛋白酶体拟肽抑制剂。它有效地抑制了HepG2和HL-60的增殖。

  DOI：

  10.1016/j.bmcl.2006.11.020

文献信息

• Structure-Based optimisation of 2-aminobenzylstatine derivatives: potent and selective inhibitors of the chymotrypsin-Like activity of the human 20S proteasome
  作者：Pascal Furet、Patricia Imbach、Peter Fuerst、Marc Lang、Maria Noorani、Johann Zimmermann、Carlos Garcı́a-Echeverrı́a

  DOI：10.1016/s0960-894x(02)00178-6

  日期：2002.5

  We have identified 2-aminobenzylstatine derivatives that inhibit non-covalently the chymotrypsin-like activity of the human 20S proteasome. A structure-based optimisation approach has allowed us to improve the potency of this structural class of proteasome inhibitors from micromolar to nanomolar level. The new derivatives showed good selectivity against the trypsin-like and post-glutamyl-peptide hydrolytic activities of this enzyme. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Design and synthesis of a novel class of furan-based molecules as potential 20S proteasome inhibitors
  作者：Yiqiu Fu、Bo Xu、Xiaomin Zou、Chao Ma、Xiaoming Yang、Ke Mou、Gang Fu、Yang Lü、Ping Xu

  DOI：10.1016/j.bmcl.2006.11.020

  日期：2007.2

  A novel class of furan-based compounds as potential 20S proteasome inhibitors have been designed and synthesized, among which nine compounds are peptide derivatives and six molecules are statine peptidomimetics. The C-terminal furanyl moiety was introduced to target molecules as furan-based amino acids. All the compounds were obtained steadily with moderate to high yield. Compound 12 was a selective

  已经设计和合成了一类新型的呋喃基化合物作为潜在的20S蛋白酶体抑制剂，其中九种化合物是肽衍生物，六种分子是他汀类肽模拟物。将C末端呋喃基部分作为基于呋喃的氨基酸引入靶分子。稳定地获得了所有化合物，产率中等至高。化合物12是选择性的中度有效的蛋白酶体拟肽抑制剂。它有效地抑制了HepG2和HL-60的增殖。
• Inhibitors of HIV-1 Proteinase Containing 2-Heterosubstituted 4-Amino-3-hydroxy-5-phenylpentanoic Acid: Synthesis, Enzyme Inhibition, and Antiviral Activity
  作者：Dieter Scholz、Andreas Billich、Brigitte Charpiot、Peter Ettmayer、Philipp Lehr、Brigitte Rosenwirth、Erwin Schreiner、Hubert Gstach

  DOI：10.1021/jm00045a013

  日期：1994.9

  A convenient procedure for the synthesis of 2-heterosubstituted statine derivatives as novel building blocks in HN-protease inhibitors has been developed. The synthesis starts with protected L-phenylalaninols, which were converted to gamma-amino alpha,beta-unsaturated esters in a one-pot procedure. A highly diastereoseletive epoxidation of the N-protected (E)-enoates, followed by regioselective ring opening of the corresponding 2,3-epoxy esters with a variety of heteronucleophiles, resulted in 2-heterosubstituted statine derivatives. The overall stereochemical outcome of the transformations meets the required configuration of HIV-protease inhibitors. The short, synthetically flexible, and highly diastereoselective synthesis of 2-heterosubstituted statines has enabled a broad derivation, covering the S3, S2, and S1'-S3' sites of the enzyme. In a series of 46 derivatives, several potent inhibitors were obtained with K-i values as low as 3.4 nM and antiviral activity in the lower nanomolar-range. The structural parameters of the compounds which determine the potency of inhibition and selectivity for the viral enzyme are discussed.