N^2.1-<(benzyloxy)carbonyl>-L-valylsarcosine | 56609-93-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: N^2.1-<(benzyloxy)carbonyl>-L-valylsarcosine
• 英文别名: N^2.1-[(benzyloxy)carbonyl]-L-valylsarcosine；N-[(Benzyloxy)carbonyl]-L-valyl-N-methylglycine；2-[methyl-[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]acetic acid
• CAS: 56609-93-9
• 化学式: C₁₆H₂₂N₂O₅
• 分子量: 322.361
• InChiKey: HWEKMKZHDLNZKR-AWEZNQCLSA-N

物化性质

• 熔点：
  128 °C
• 沸点：
  529.9±45.0 °C(Predicted)
• 密度：
  1.210±0.06 g/cm3(Predicted)

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：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N^2.1-<(benzyloxy)carbonyl>-L-valylsarcosine 在 palladium on activated charcoal 氢气 、 三乙胺 、 N,N'-羰基二咪唑 作用下， 以 乙醇 为溶剂， 25.0 ℃ 、310.27 kPa 条件下， 反应 21.0h， 生成
  参考文献：
  名称：

  Inhibition of human leukocyte elastase (HLE) by N-substituted peptidyl trifluoromethyl ketones

  摘要：

  A series of tripeptides possessing trifluoromethyl or aryl ketone residues at P1 were prepared and evaluated both in vitro and in vivo as potential inhibitors of human leukocyte elastase (HLE). Tripeptides containing non naturally occurring N-substituted glycine residues at the P2-position have been demonstrated to be potent in vitro inhibitors of HLE, with IC50 values in the submicromolar range. Sterically demanding substituents on the P2-nitrogen have no detrimental effect on in vitro potency. The inhibition process presumably acts via hemiketal formation with the active site Ser195 of HLE, and is facilitated by the strongly electron withdrawing trifluoromethyl functionality. Deletion of the amino acid at the P3-subsite region affords inactive compounds. Valine is the preferred residue at the P1-position, whereas the corresponding glycine, alanine, alpha,alpha-dimethylglycine, or phenylalanine analogues are all inactive. The compounds described herein all confer a high degree of in vitro specificity when tested against representative cysteine, aspartyl, metallo, and other serine proteases. One of the most potent in vitro inhibitors is (3RS)-N-[4-[[[(4-chlorophenyl)sulfonyl]amino]carbonyl]phenyl]oxomethyl]-L-valyl-N-(2,3-dihydro-1H-inden-2-yl)glycine N-[3-(1,1,1-trifluoro-4-methyl-2-oxopentyl)]amide (20i; BI-RA-260) (IC50 = 0.084-mu-M). Compound 20i was also tested in hamsters in an elastase-induced pulmonary hemorrhage (EPH) model. In this model, intratracheal (it.) administration of 20i, 5 min prior to HLE challenge, effectively inhibited hemorrhage in a dose-dependent manner with an ED50 of 4.8-mu-g. The inhibitor 20i, 20-mu-g administered it. 24, 48, and 72 h prior to HLE challenge, exhibits significant inhibition against hemorrhage at all time points (97%, 64% and 49%, respectively). In a 21-day chronic model of emphysema in hamsters, 200-mu-g of HLE administered it. caused an elastase-induced emphysema in the lungs which can be quantitated histologically utilizing image analysis. In this assay, 20i significantly inhibited pulmonary lesions associated with septal destruction and increased alveolar spaces, when dosed at 20-mu-g it. 5 min prior to challenge with HLE.

  DOI：

  10.1021/jm00082a005
• 作为产物：
  描述：

  CBZ-L-缬氨酸 在 sodium hydroxide 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 水 为溶剂， 反应 14.0h， 生成 N^2.1-<(benzyloxy)carbonyl>-L-valylsarcosine
  参考文献：
  名称：

  通过受保护的（脱羧-二肽基）膦酸酯的C-烷基化反应，用膦酸酯代替羧基末端的二肽衍生物†

  摘要：

  由ZL-丙氨酸（1a）制备具有Z-保护的具有（脱羧肌氨酸基）膦酸酯部分的二苯基（脱羧-二肽基）膦酸酯5a - c。ZL-缬氨酸（1B），和ZL -苯丙氨酸（1C）由以下一系列步骤：用甲基肌氨酸盐偶合（图2a - C ^），皂化（图3a - Ç），Hofer的-MOEST氧化decarboxyiation通过电解在MeOH（4A - c），与Arbuzov反应与P（OPh）3 / TiCl 4（方案3）。双去质子化和烷基化导致侧链旁边的膦酸酯基团的非立体选择性的掺入（类型的产品6 - 8，9个的实例，参见方案4）。在6a – c和8c的情况下，可以分离非对映异构体，并推论新形成的立体异构中心的构型。我们将L，D-构型分配给31 P-NMR信号出现在较高场的非对映异构体。

  DOI：

  10.1002/hlca.19910740702

文献信息

• Dipeptide Derivatives with a Phosphonate Instead of Carboxylate Terminus byC-Alkylation of Protected (Decarboxy-dipeptidyl)phosphonates
  作者：Christian Gerber、Dieter Seebach

  DOI：10.1002/hlca.19910740702

  日期：1991.10.30

  Z-Protected diphenyl (decarboxy-dipeptidyl)phosphonates 5a-c with a (decarboxysarcosinyl)phosphonate moiety are prepared from Z-L-alanine (1a). Z-L-valine (1b), and Z-L-phenylalanine (1c) by the following series of steps: coupling with methyl sarcosinate (2a–c), saponification (3a–c), Hofer-Moest oxidative decarboxyiation by electrolysis in MeOH (4a–c), and Arbuzov reaction with P(OPh)3/TiCl4 (Scheme

  由ZL-丙氨酸（1a）制备具有Z-保护的具有（脱羧肌氨酸基）膦酸酯部分的二苯基（脱羧-二肽基）膦酸酯5a - c。ZL-缬氨酸（1B），和ZL -苯丙氨酸（1C）由以下一系列步骤：用甲基肌氨酸盐偶合（图2a - C ^），皂化（图3a - Ç），Hofer的-MOEST氧化decarboxyiation通过电解在MeOH（4A - c），与Arbuzov反应与P（OPh）3 / TiCl 4（方案3）。双去质子化和烷基化导致侧链旁边的膦酸酯基团的非立体选择性的掺入（类型的产品6 - 8，9个的实例，参见方案4）。在6a – c和8c的情况下，可以分离非对映异构体，并推论新形成的立体异构中心的构型。我们将L，D-构型分配给31 P-NMR信号出现在较高场的非对映异构体。
• EP0863915B1
  申请人：——

  公开号：EP0863915B1

  公开（公告）日：2000-02-02
• ACYLATED ENOL DERIVATIVES OF $g(a)-KETOESTERS AND $g(a)-KETOAMIDES
  申请人：HOECHST MARION ROUSSEL, INC.

  公开号：EP0863915A1

  公开（公告）日：1998-09-16
• US5948886A
  申请人：——

  公开号：US5948886A

  公开（公告）日：1999-09-07
• US6172044B1
  申请人：——

  公开号：US6172044B1

  公开（公告）日：2001-01-09