N-(tert-butyloxycarbonyl)-2-methylamino-4-cyano-L-butyric acid | 161561-59-7

• 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: N-(tert-butyloxycarbonyl)-2-methylamino-4-cyano-L-butyric acid
• 英文别名: (2S)-2-[(tert-butoxycarbonyl)(methyl)amino]-4-cyanobutyric acid；(2S)-4-cyano-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butanoic acid
• CAS: 161561-59-7
• 化学式: C₁₁H₁₈N₂O₄
• 分子量: 242.275
• InChiKey: QQIRVCGKPTZFTB-QMMMGPOBSA-N

物化性质

• 熔点：
  86.2-87.6 °C
• 沸点：
  403.9±45.0 °C(Predicted)
• 密度：
  1.157±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  90.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(tert-butyloxycarbonyl)-2-methylamino-4-cyano-L-butyric acid 在 palladium hydroxide - carbon 氢气 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 40.0 ℃ 、101.33 kPa 条件下， 生成 tert-butyl (2S,4R)-4-((S)-2-((tert-butoxycarbonyl)(methyl)amino)-5-(3-nitroguanidino)pentanamido)-2-carbamoylpyrrolidine-1-carboxylate
  参考文献：
  名称：

  Selective l-nitroargininylaminopyrrolidine and l-nitroargininylaminopiperidine neuronal nitric oxide synthase inhibitors

  摘要：

  Selective inhibition of the localized excess production of NO by neuronal nitric oxide synthase (nNOS) has been targeted as a potential means of treating various neurological disorders. Based on observations from the X-ray crystal structures of complexes of nNOS with two nNOS-selective inhibitors, (4S)-N-{4-amino-5-[(2-amino)ethylamino]pentyl}-N'-nitroguanidine (L-Arg(NO2)-L-Dbu-NH2 (1) and 4-N-(N-omega-nitro-L-argininyl)-trans-4-amino-L-proline amide (2), a series of descarboxamide analogues was designed and synthesized (3-7). The most potent compound was aminopyrrolidine analogue 3, which exhibited better potency and selectivity for nNOS than parent compound 2. In addition, 3 provided higher lipophilicity and a lower molecular weight than 2, therefore having better physicochemical properties. N-alpha-Methylated analogues (8-11) also were prepared for increased lipophilicity of the inhibitors, but they had 4- to 5-fold weaker binding affinity compared to their parent compounds. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.01.001
• 作为产物：
  描述：

  Boc-L-谷氨酰胺 在 乙酸酐 、 sodium hydride 作用下， 以 四氢呋喃 、 吡啶 为溶剂， 生成 N-(tert-butyloxycarbonyl)-2-methylamino-4-cyano-L-butyric acid
  参考文献：
  名称：

  的新颖的合成ñ α -甲基精氨酸和Ñ α -甲基-鸟氨酸衍生物

  摘要：

  Ñ α -Boc- Ñ α甲基Ñ ω，ω ' -双（苄氧羰基） -大号-精氨酸和Ñ α -Boc- Ñ α甲基Ñ δ苄氧基羰基大号鸟氨酸开始的Boc-已经合成L- Gln。将Boc- L -Gln的γ-羧酰胺脱水成腈基，然后将生成的化合物选择性地甲基化，得到N -Boc-2-甲基氨基-4-氰基丁酸。然后将腈还原成胺家具关键中间体Ñ α -Boc-Ñ α甲基大号鸟氨酸。

  DOI：

  10.1016/0040-4039(94)02210-3

文献信息

• Novel synthesis of Nα-methyl-arginine and Nα-methyl-ornithine derivatives
  作者：Chu-Biao Xue、William F. DeGrado

  DOI：10.1016/0040-4039(94)02210-3

  日期：1995.1

  Nα-Boc-Nα-methyl-Nω,ω′-bis(benzyloxycarbonyl)-L-arginine and Nα-Boc-Nα-methyl-Nδ-benzyloxycarbonyl-L-ornithine have been synthesized starting with Boc-L-Gln. The γ-carboxamide of Boc-L-Gln was dehydrated to a nitrile group and the resulting compound is selectively methylated providing N-Boc-2-methylamino-4-cyanobutyric acid. The nitrile is then reduced to an amine furnishing the key intermediate N

  Ñ α -Boc- Ñ α甲基Ñ ω，ω ' -双（苄氧羰基） -大号-精氨酸和Ñ α -Boc- Ñ α甲基Ñ δ苄氧基羰基大号鸟氨酸开始的Boc-已经合成L- Gln。将Boc- L -Gln的γ-羧酰胺脱水成腈基，然后将生成的化合物选择性地甲基化，得到N -Boc-2-甲基氨基-4-氰基丁酸。然后将腈还原成胺家具关键中间体Ñ α -Boc-Ñ α甲基大号鸟氨酸。
• Synthesis of cyclic and acyclic Nα-methyl-Nω-alkyl-l-arginine analogues
  作者：Kyle P. Kokko、H. Brooks Hooper、Thomas A. Dix

  DOI：10.1016/j.tetlet.2004.01.047

  日期：2004.3

  A series of Nalpha-methyl-alkyl-L-arginine (Arg) analogues have been synthesized from inexpensive, commercially available starting rnaterials. These analogues, once incorporated into pharmaceutically relevant peptides, are expected to increase binding affinity, receptor selectivity, lipophificity, and stability Lis demonstrated With analogues of similar design and Structure. (C) 2001 Published by Elsevier Ltd.
• Selective l-nitroargininylaminopyrrolidine and l-nitroargininylaminopiperidine neuronal nitric oxide synthase inhibitors
  作者：Jiwon Seo、Pavel Martásek、Linda J. Roman、Richard B. Silverman

  DOI：10.1016/j.bmc.2007.01.001

  日期：2007.3

  Selective inhibition of the localized excess production of NO by neuronal nitric oxide synthase (nNOS) has been targeted as a potential means of treating various neurological disorders. Based on observations from the X-ray crystal structures of complexes of nNOS with two nNOS-selective inhibitors, (4S)-N-4-amino-5-[(2-amino)ethylamino]pentyl}-N'-nitroguanidine (L-Arg(NO2)-L-Dbu-NH2 (1) and 4-N-(N-omega-nitro-L-argininyl)-trans-4-amino-L-proline amide (2), a series of descarboxamide analogues was designed and synthesized (3-7). The most potent compound was aminopyrrolidine analogue 3, which exhibited better potency and selectivity for nNOS than parent compound 2. In addition, 3 provided higher lipophilicity and a lower molecular weight than 2, therefore having better physicochemical properties. N-alpha-Methylated analogues (8-11) also were prepared for increased lipophilicity of the inhibitors, but they had 4- to 5-fold weaker binding affinity compared to their parent compounds. (c) 2007 Elsevier Ltd. All rights reserved.