2,3,5-trichloro-4-iodo-6-methoxyaniline | 244037-15-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2,3,5-trichloro-4-iodo-6-methoxyaniline
• CAS: 244037-15-8
• 化学式: C₇H₅Cl₃INO
• 分子量: 352.386
• InChiKey: XBSDTZPJOCDARY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.84
• 重原子数：
  13.0
• 可旋转键数：
  1.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  35.25
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  2,3,5-trichloro-4-iodo-6-methoxyaniline 在 铜 、 亚硝酸异戊酯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 120.5h， 生成 2,2',3,3',6,6'-hexachloro-5,5'-dimethoxy-1,1'-biphenyl
  参考文献：
  名称：

  2,2‘,3,3‘,6,6‘-Hexachlorobiphenyl Hydroxylation by Active Site Mutants of Cytochrome P450 2B1 and 2B11

  摘要：

  The structural basis of species differences in cytochrome P450 2B-mediated hydroxylation of 2,2',3,3',6,6'-hexachlorobiphenyl (236HCB) was evaluated by using 14 site-directed mutants of cytochrome P450 2B1 and three point mutants of 2B11 expressed in Escherichia coli, To facilitate metabolite identification, seven possible products, including three hydroxylated and four dihydroxylated hexachlorobiphenyls, were synthesized by direct functionalization of precursors and Ullmann and crossed Ullmann reactions, HPLC and GC/MS analysis and comparison with authentic standards revealed that 2B1 2B11, and all their mutants produced 4,5-dihydroxy-236HCB and 5-hydroxy-236HCB, while 2B11 L363V and 2B1 I114V mutants also catalyzed hydroxylation at the 4-position. The amount of products formed by 2B1 mutants I114V, F206L, L209A, T302S, V363A, V363L, V367A, I477A, I477L, G478S, I480A, and I480L was smaller than that of the wild type. I477V exhibited unaltered 236HCB metabolism, and I480V produced twice as much dihydroxy product as the wild type, For 2B11, substitution of Val-114 or Asp-290 with lie decreased the product yields. Replacement of Leu-363 with Val dramatically altered the profile of 236HCB metabolites. In addition to an increase in the overall level of hydroxylation, the mutant mainly catalyzed hydroxylation at the 4-position. Incubation of P450 2B1 with 5-hydroxy-236HCB produced 4,5-dihydroxy-236HCB, which indicates that 4,5-dihydroxy-236HCB may be formed by a direct hydroxylation of 5-hydroxy-236HCB. The findings from this study demonstrate the importance of residues 114, 206, 209, 302, 363, 367, 477, 478, and 480 in 2B1 and 114, 290, and 363 in 2B11 for 236HCB metabolism.

  DOI：

  10.1021/tx990030j
• 作为产物：
  描述：

  3,4,6-三氯-2-硝基苯甲醚 在 sodium dithionite 、 N,N,N-trimethylbenzenemethanaminium dichloroiodate 、 zinc(II) chloride 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 反应 20.0h， 生成 2,3,5-trichloro-4-iodo-6-methoxyaniline
  参考文献：
  名称：

  2,2‘,3,3‘,6,6‘-Hexachlorobiphenyl Hydroxylation by Active Site Mutants of Cytochrome P450 2B1 and 2B11

  摘要：

  The structural basis of species differences in cytochrome P450 2B-mediated hydroxylation of 2,2',3,3',6,6'-hexachlorobiphenyl (236HCB) was evaluated by using 14 site-directed mutants of cytochrome P450 2B1 and three point mutants of 2B11 expressed in Escherichia coli, To facilitate metabolite identification, seven possible products, including three hydroxylated and four dihydroxylated hexachlorobiphenyls, were synthesized by direct functionalization of precursors and Ullmann and crossed Ullmann reactions, HPLC and GC/MS analysis and comparison with authentic standards revealed that 2B1 2B11, and all their mutants produced 4,5-dihydroxy-236HCB and 5-hydroxy-236HCB, while 2B11 L363V and 2B1 I114V mutants also catalyzed hydroxylation at the 4-position. The amount of products formed by 2B1 mutants I114V, F206L, L209A, T302S, V363A, V363L, V367A, I477A, I477L, G478S, I480A, and I480L was smaller than that of the wild type. I477V exhibited unaltered 236HCB metabolism, and I480V produced twice as much dihydroxy product as the wild type, For 2B11, substitution of Val-114 or Asp-290 with lie decreased the product yields. Replacement of Leu-363 with Val dramatically altered the profile of 236HCB metabolites. In addition to an increase in the overall level of hydroxylation, the mutant mainly catalyzed hydroxylation at the 4-position. Incubation of P450 2B1 with 5-hydroxy-236HCB produced 4,5-dihydroxy-236HCB, which indicates that 4,5-dihydroxy-236HCB may be formed by a direct hydroxylation of 5-hydroxy-236HCB. The findings from this study demonstrate the importance of residues 114, 206, 209, 302, 363, 367, 477, 478, and 480 in 2B1 and 114, 290, and 363 in 2B11 for 236HCB metabolism.

  DOI：

  10.1021/tx990030j