(2S,3S)-2-amino-N-((S)-1-hydroxy-3-phenyl-propan-2-yl)-3-methyl-pentanamide | 742675-58-7

• 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: (2S,3S)-2-amino-N-((S)-1-hydroxy-3-phenyl-propan-2-yl)-3-methyl-pentanamide
• 英文别名: (2S,3S)-2-amino-N-((S)-1-hydroxy-3-phenylpropan-2-yl)-3-methylpentanamide；(2S,3S)-2-amino-N-[(2S)-1-hydroxy-3-phenylpropan-2-yl]-3-methylpentanamide
• CAS: 742675-58-7
• 化学式: C₁₅H₂₄N₂O₂
• 分子量: 264.368
• InChiKey: VSAQCXYUHOTNJS-UBHSHLNASA-N

物化性质

• 沸点：
  485.6±45.0 °C(Predicted)
• 密度：
  1.074±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  75.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S,3S)-2-amino-N-((S)-1-hydroxy-3-phenyl-propan-2-yl)-3-methyl-pentanamide 在 4-二甲氨基吡啶 、 pyridine-SO3 complex 、 二甲基亚砜 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.83h， 生成 (2S,3S)-3-methyl-2-(naphthalen-1-ylsulfonylamino)-N-[(2S)-1-oxo-3-phenylpropan-2-yl]pentanamide
  参考文献：
  名称：

  Synthesis of Peptide Aldehyde Derivatives as Selective Inhibitors of Human Cathepsin L and Their Inhibitory Effect on Bone Resorption

  摘要：

  Cathepsin L, a lysosomal cysteine protease, is secreted by osteoclasts and participates in bone collagen degradation. In a search for cathepsin L inhibitors as antiosteoporotic agents, a series of peptide aldehyde derivatives were prepared by two synthetic approaches, DMSO oxidation of the corresponding alcohol derivatives and DIBAL-H reduction of the corresponding N,O-dimethylhydroxylamide derivatives, and evaluated for inhibitory activity against human cathepsin L and for inhibitory effects on bone resorption. Some of the peptide aldehyde derivatives including alpha-acylamino aldehyde derivatives showed potent activities. Among these compounds, N-(1-naphthalenylsulfonyl-L-isoleucyl-L-tryptophanal (12) was selected as a candidate for further investigation. Compound 12, a potent, selective, and reversible inhibitor of human cathepsin L with an IC50 Of 1.9 nM, inhibited the release of Ca2+ and hydroxyproline from bone in in vitro bone culture system and also prevented bone loss in ovariectomized mice at an oral dose of 50 mg/kg.

  DOI：

  10.1021/jm9803065
• 作为产物：
  描述：

  Z-L-苯丙氨醇 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 20.0h， 生成 (2S,3S)-2-amino-N-((S)-1-hydroxy-3-phenyl-propan-2-yl)-3-methyl-pentanamide
  参考文献：
  名称：

  Synthesis of Peptide Aldehyde Derivatives as Selective Inhibitors of Human Cathepsin L and Their Inhibitory Effect on Bone Resorption

  摘要：

  Cathepsin L, a lysosomal cysteine protease, is secreted by osteoclasts and participates in bone collagen degradation. In a search for cathepsin L inhibitors as antiosteoporotic agents, a series of peptide aldehyde derivatives were prepared by two synthetic approaches, DMSO oxidation of the corresponding alcohol derivatives and DIBAL-H reduction of the corresponding N,O-dimethylhydroxylamide derivatives, and evaluated for inhibitory activity against human cathepsin L and for inhibitory effects on bone resorption. Some of the peptide aldehyde derivatives including alpha-acylamino aldehyde derivatives showed potent activities. Among these compounds, N-(1-naphthalenylsulfonyl-L-isoleucyl-L-tryptophanal (12) was selected as a candidate for further investigation. Compound 12, a potent, selective, and reversible inhibitor of human cathepsin L with an IC50 Of 1.9 nM, inhibited the release of Ca2+ and hydroxyproline from bone in in vitro bone culture system and also prevented bone loss in ovariectomized mice at an oral dose of 50 mg/kg.

  DOI：

  10.1021/jm9803065
• 作为试剂：
  描述：

  联苯单乙酮 、 3-hydroxy-5-methyl-3-(trifluoromethyl)-2,3-dihydrobenzo[d]isothiazole 1,1-dioxide 在 (2S,3S)-2-amino-N-((S)-1-hydroxy-3-phenyl-propan-2-yl)-3-methyl-pentanamide 、 2,6-二氟苯甲酸 作用下， 以 氯仿 为溶剂， 反应 60.0h， 以91%的产率得到(R)-1-([1,1'-biphenyl]-4-yl)-2-(5-methyl-1,1-dioxido-3-(trifluoromethyl)-2,3-dihydrobenzo[d]isothiazol-3-yl)ethanone
  参考文献：
  名称：

  未保护的半胱氨酸与酮的有机催化脱水曼尼希反应可高度对映选择性地构建氟代烷基化的立体立体中心。

  摘要：

  报道了氟代烷基半缩醛与酮的一般有机催化不对称脱水曼尼希反应。在该曼尼希反应中，以前较少探索的芳基酮显示出很高的反应活性。通过这种有效的方法，直接获得了广泛的生物活性β-氨基酮。更重要的是，通过19 F NMR和HRMS分析检测并鉴定了参与反应的两种不同中间体。此外，通过生物活性的氟烷基β-氨基醇的合成证明了产物的合成效用。

  DOI：

  10.1021/acs.orglett.5b02514

文献信息

• Highly Enantioselective Construction of Fluoroalkylated Quaternary Stereocenters via Organocatalytic Dehydrated Mannich Reaction of Unprotected Hemiaminals with Ketones
  作者：Sheng Zhang、Lijun Li、Yanbin Hu、Yanan Li、Yu Yang、Zhenggen Zha、Zhiyong Wang

  DOI：10.1021/acs.orglett.5b02514

  日期：2015.10.16

  organocatalytic asymmetric dehydrated Mannich reaction of fluoroalkyl hemiaminals with ketones is reported. In this Mannich reaction, previously less explored aryl ketones showed great reactivity. By virtue of this efficient method, a wide range of biologically active β-amino ketones were directly obtained. More importantly, two different intermediates involved in the reaction were detected and identified by 19F

  报道了氟代烷基半缩醛与酮的一般有机催化不对称脱水曼尼希反应。在该曼尼希反应中，以前较少探索的芳基酮显示出很高的反应活性。通过这种有效的方法，直接获得了广泛的生物活性β-氨基酮。更重要的是，通过19 F NMR和HRMS分析检测并鉴定了参与反应的两种不同中间体。此外，通过生物活性的氟烷基β-氨基醇的合成证明了产物的合成效用。
• Synthesis of Peptide Aldehyde Derivatives as Selective Inhibitors of Human Cathepsin L and Their Inhibitory Effect on Bone Resorption
  作者：Tsuneo Yasuma、Satoru Oi、Nobuo Choh、Toshiyuki Nomura、Naoki Furuyama、Atsushi Nishimura、Yukio Fujisawa、Takashi Sohda

  DOI：10.1021/jm9803065

  日期：1998.10.1

  Cathepsin L, a lysosomal cysteine protease, is secreted by osteoclasts and participates in bone collagen degradation. In a search for cathepsin L inhibitors as antiosteoporotic agents, a series of peptide aldehyde derivatives were prepared by two synthetic approaches, DMSO oxidation of the corresponding alcohol derivatives and DIBAL-H reduction of the corresponding N,O-dimethylhydroxylamide derivatives, and evaluated for inhibitory activity against human cathepsin L and for inhibitory effects on bone resorption. Some of the peptide aldehyde derivatives including alpha-acylamino aldehyde derivatives showed potent activities. Among these compounds, N-(1-naphthalenylsulfonyl-L-isoleucyl-L-tryptophanal (12) was selected as a candidate for further investigation. Compound 12, a potent, selective, and reversible inhibitor of human cathepsin L with an IC50 Of 1.9 nM, inhibited the release of Ca2+ and hydroxyproline from bone in in vitro bone culture system and also prevented bone loss in ovariectomized mice at an oral dose of 50 mg/kg.