N^α-Acetyl-N^τ-(p-nitrophenyl)-L-histidine methyl ester | 154061-60-6

• 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^α-Acetyl-N^τ-(p-nitrophenyl)-L-histidine methyl ester
• 英文别名: methyl (2S)-2-acetamido-3-[1-(4-nitrophenyl)imidazol-4-yl]propanoate
• CAS: 154061-60-6
• 化学式: C₁₅H₁₆N₄O₅
• 分子量: 332.316
• InChiKey: ZGLTXDQFZRHDOK-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N^α-Acetyl-N^τ-(p-nitrophenyl)-L-histidine methyl ester 在 tin(ll) chloride 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以74%的产率得到N^α-Acetyl-N^τ-(p-aminophenyl)-L-histidine methyl ester
  参考文献：
  名称：

  Synthesis of N.epsilon.-(p-Bromophenyl)-L-lysine and N.tau.-(p-Bromophenyl)-L-histidine as Models for Adducts of Bromobenzene 3,4-Oxide to Protein. Observation of an Unusual Pd-Catalyzed N.tau. to N.pi.-Aryl Substituent Migration

  摘要：

  Bromobenzene 3,4-oxide (1), the putative toxic metabolite of bromobenzene, is known to alkylate protein sulfur nucleophiles in vivo and is postulated to alkylate protein nitrogen nucleophiles, the expected products of which would include, after hydrolysis, N(t)au-(p-bromophenyl)-L-histidine (8) and N(e)psilon- (p-bromophenyl)-L-lysine (7). These non-proteinogenic amino acids have now been synthesized by unambiguous routes and their stability under protein hydrolysis conditions demonstrated. Treatment of N-alpha-Cbz-lysine with sodium nitroprusside gave the epsilon-lysinol derivative, which by successive treatment with CBr4/Ph(3)P and excess p-bromoaniline and deprotection (6.0 M HCl, 110 degrees C) afforded an overall 14% yield of 7. Alkylation of N alpha-Ac-L-histidine methyl ester with p-fluoronitrobenzene, followed by reduction, a modified Sandmeyer bromo-dediazotization (tert-BuONO/CuBr2), and deprotection afforded 8 in 10% overall yield. An unexpected N(t)au- to N(p)i-aryl migration was observed during hydrogenation of a N(t)au-(p-nitrophenyl)histidine derivative over Pd/charcoal; it was avoided by use of SnCl2/ethanol for nitro reduction. The N alpha-acetyl derivatives of 7 and 8, of interest as haptens for use in raising antibodies against proteins alkylated by epoxide 1, were also prepared and characterized.

  DOI：

  10.1021/jo00083a011
• 作为产物：
  描述：

  对氟硝基苯 、 乙酰基-L-组氨酸 甲基 酯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 以68%的产率得到N^α-Acetyl-N^τ-(p-nitrophenyl)-L-histidine methyl ester
  参考文献：
  名称：

  Synthesis of N.epsilon.-(p-Bromophenyl)-L-lysine and N.tau.-(p-Bromophenyl)-L-histidine as Models for Adducts of Bromobenzene 3,4-Oxide to Protein. Observation of an Unusual Pd-Catalyzed N.tau. to N.pi.-Aryl Substituent Migration

  摘要：

  Bromobenzene 3,4-oxide (1), the putative toxic metabolite of bromobenzene, is known to alkylate protein sulfur nucleophiles in vivo and is postulated to alkylate protein nitrogen nucleophiles, the expected products of which would include, after hydrolysis, N(t)au-(p-bromophenyl)-L-histidine (8) and N(e)psilon- (p-bromophenyl)-L-lysine (7). These non-proteinogenic amino acids have now been synthesized by unambiguous routes and their stability under protein hydrolysis conditions demonstrated. Treatment of N-alpha-Cbz-lysine with sodium nitroprusside gave the epsilon-lysinol derivative, which by successive treatment with CBr4/Ph(3)P and excess p-bromoaniline and deprotection (6.0 M HCl, 110 degrees C) afforded an overall 14% yield of 7. Alkylation of N alpha-Ac-L-histidine methyl ester with p-fluoronitrobenzene, followed by reduction, a modified Sandmeyer bromo-dediazotization (tert-BuONO/CuBr2), and deprotection afforded 8 in 10% overall yield. An unexpected N(t)au- to N(p)i-aryl migration was observed during hydrogenation of a N(t)au-(p-nitrophenyl)histidine derivative over Pd/charcoal; it was avoided by use of SnCl2/ethanol for nitro reduction. The N alpha-acetyl derivatives of 7 and 8, of interest as haptens for use in raising antibodies against proteins alkylated by epoxide 1, were also prepared and characterized.

  DOI：

  10.1021/jo00083a011

文献信息

• Synthesis of N.epsilon.-(p-Bromophenyl)-L-lysine and N.tau.-(p-Bromophenyl)-L-histidine as Models for Adducts of Bromobenzene 3,4-Oxide to Protein. Observation of an Unusual Pd-Catalyzed N.tau. to N.pi.-Aryl Substituent Migration
  作者：Ramesh Bambal、Robert P. Hanzlik

  DOI：10.1021/jo00083a011

  日期：1994.2

  Bromobenzene 3,4-oxide (1), the putative toxic metabolite of bromobenzene, is known to alkylate protein sulfur nucleophiles in vivo and is postulated to alkylate protein nitrogen nucleophiles, the expected products of which would include, after hydrolysis, N(t)au-(p-bromophenyl)-L-histidine (8) and N(e)psilon- (p-bromophenyl)-L-lysine (7). These non-proteinogenic amino acids have now been synthesized by unambiguous routes and their stability under protein hydrolysis conditions demonstrated. Treatment of N-alpha-Cbz-lysine with sodium nitroprusside gave the epsilon-lysinol derivative, which by successive treatment with CBr4/Ph(3)P and excess p-bromoaniline and deprotection (6.0 M HCl, 110 degrees C) afforded an overall 14% yield of 7. Alkylation of N alpha-Ac-L-histidine methyl ester with p-fluoronitrobenzene, followed by reduction, a modified Sandmeyer bromo-dediazotization (tert-BuONO/CuBr2), and deprotection afforded 8 in 10% overall yield. An unexpected N(t)au- to N(p)i-aryl migration was observed during hydrogenation of a N(t)au-(p-nitrophenyl)histidine derivative over Pd/charcoal; it was avoided by use of SnCl2/ethanol for nitro reduction. The N alpha-acetyl derivatives of 7 and 8, of interest as haptens for use in raising antibodies against proteins alkylated by epoxide 1, were also prepared and characterized.