叔-丁基N-[3-(亚氨乙酰基氨基甲基)苄基]氨基甲酸酯,盐酸盐 | 180001-98-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 叔-丁基N-[3-(亚氨乙酰基氨基甲基)苄基]氨基甲酸酯,盐酸盐
• 中文别名: [[3-[[(1-亚氨基乙基)氨基]甲基]苯基]甲基]甲酰胺酸1,1-二甲基乙酯单盐酸盐
• 英文名称: N-(3-(N-Boc-aminomethyl)benzyl)acetimidine hydrochloride
• 英文别名: tert-Butyl N-[3-(Acetimidoylaminomethyl)benzyl]carbamate, Hydrochloride；tert-butyl N-[[3-[(1-aminoethylideneamino)methyl]phenyl]methyl]carbamate;hydrochloride
• CAS: 180001-98-3
• 化学式: C₁₅H₂₃N₃O₂*ClH
• 分子量: 313.827
• InChiKey: LTLBLVCQQFRNNL-UHFFFAOYSA-N

物化性质

• 溶解度：
  可溶于DMF、乙醇、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  3.01
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  76.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  叔-丁基N-[3-(亚氨乙酰基氨基甲基)苄基]氨基甲酸酯,盐酸盐 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以98%的产率得到N-[3-(氨甲基)苄基]乙脒
  参考文献：
  名称：

  Mechanism of Inactivation of Inducible Nitric Oxide Synthase by Amidines. Irreversible Enzyme Inactivation without Inactivator Modification

  摘要：

  Nitric oxide synthases (NOS) are hemoproteins that catalyze the reaction Of L-arginine to L-Citrulline and nitric oxide. N-(3-(Aminomethyl)benzyl)acetamidine (1400W) was reported to be a slow, tight-binding, and highly selective inhibitor of iNOS in vitro and in vivo. Previous mechanistic studies reported that 1400W was recovered quantitatively after iNOS fully lost its activity and modification to iNOS was not detected. Here, it is shown that 1400W is a time-, concentration-, and NADPH-dependent irreversible inactivator of iNOS. HPLC-electrospray mass spectrometric analysis of the incubation mixture of iNOS with 1400W shows both loss of heme cofactor and formation of bilivedin, as was previously observed for iNOS inactivation by another amidine-containing compound, N-5(1-iminoethyl)-L-ornithine (L-NIO). The amount of biliverdin produced corresponds to the amount of heme lost by 1400W inactivation of iNOS. A convenient MS/MS-HPLC methodology was developed to identify the trace amount of biliverdin produced by inactivation of iNOS with either 1400W or L-NIO to be biliverdin \Xalpha out of the four possible regioisomers. Two mechanisms were previously proposed for iNOS inactivation by L-NIO: (1) uncoupling of the heme peroxide intermediate, leading to destruction of the heme to biliverdin; (2) abstraction of a hydrogen atom from the amidine methyl group followed by attachment to the heme cofactor, which causes the enzyme to catalyze the heme oxygenase reaction. The second mechanistic proposal was ruled out by inactivation of iNOS with d(3)-1400W, which produced no d(2)-1400W. Detection of carbon monoxide as one of the heme-degradation products further excludes the covalent heme adduct mechanism. On the basis of these results, a third mechanism is proposed in which the amidine inactivators of iNOS bind as does substrate L-arginine, but because of the amidine methyl group, the heme peroxy intermediate cannot be protonated, thereby preventing its conversion to the heme oxo intermediate. This leads to a change in the enzyme mechanism to one that resembles that of heme oxygenase, an enzyme known to convert heme to biliverdin \Xalpha.. This appears to be the first example of a compound that causes irreversible inactivation of an enzyme without itself becoming modified in any way.

  DOI：

  10.1021/ja0445645
• 作为产物：
  描述：

  乙基乙酰亚胺盐酸盐 、 N-[3-(氨基甲基)苄基]氨基甲酸叔丁酯 以 乙醇 为溶剂， 反应 3.0h， 以92%的产率得到叔-丁基N-[3-(亚氨乙酰基氨基甲基)苄基]氨基甲酸酯,盐酸盐
  参考文献：
  名称：

  Mechanism of Inactivation of Inducible Nitric Oxide Synthase by Amidines. Irreversible Enzyme Inactivation without Inactivator Modification

  摘要：

  Nitric oxide synthases (NOS) are hemoproteins that catalyze the reaction Of L-arginine to L-Citrulline and nitric oxide. N-(3-(Aminomethyl)benzyl)acetamidine (1400W) was reported to be a slow, tight-binding, and highly selective inhibitor of iNOS in vitro and in vivo. Previous mechanistic studies reported that 1400W was recovered quantitatively after iNOS fully lost its activity and modification to iNOS was not detected. Here, it is shown that 1400W is a time-, concentration-, and NADPH-dependent irreversible inactivator of iNOS. HPLC-electrospray mass spectrometric analysis of the incubation mixture of iNOS with 1400W shows both loss of heme cofactor and formation of bilivedin, as was previously observed for iNOS inactivation by another amidine-containing compound, N-5(1-iminoethyl)-L-ornithine (L-NIO). The amount of biliverdin produced corresponds to the amount of heme lost by 1400W inactivation of iNOS. A convenient MS/MS-HPLC methodology was developed to identify the trace amount of biliverdin produced by inactivation of iNOS with either 1400W or L-NIO to be biliverdin \Xalpha out of the four possible regioisomers. Two mechanisms were previously proposed for iNOS inactivation by L-NIO: (1) uncoupling of the heme peroxide intermediate, leading to destruction of the heme to biliverdin; (2) abstraction of a hydrogen atom from the amidine methyl group followed by attachment to the heme cofactor, which causes the enzyme to catalyze the heme oxygenase reaction. The second mechanistic proposal was ruled out by inactivation of iNOS with d(3)-1400W, which produced no d(2)-1400W. Detection of carbon monoxide as one of the heme-degradation products further excludes the covalent heme adduct mechanism. On the basis of these results, a third mechanism is proposed in which the amidine inactivators of iNOS bind as does substrate L-arginine, but because of the amidine methyl group, the heme peroxy intermediate cannot be protonated, thereby preventing its conversion to the heme oxo intermediate. This leads to a change in the enzyme mechanism to one that resembles that of heme oxygenase, an enzyme known to convert heme to biliverdin \Xalpha.. This appears to be the first example of a compound that causes irreversible inactivation of an enzyme without itself becoming modified in any way.

  DOI：

  10.1021/ja0445645