5'-(tert-butoxycarbonyl)-3-(2-chloroethyl)-4'-(2-methoxycarbonylethyl)-3',4-dimethyl-2,2'-dipyrrylmethane-5-carboxylic acid | 157528-35-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 5'-(tert-butoxycarbonyl)-3-(2-chloroethyl)-4'-(2-methoxycarbonylethyl)-3',4-dimethyl-2,2'-dipyrrylmethane-5-carboxylic acid
• 英文别名: 4-(2-chloroethyl)-5-[[4-(3-methoxy-3-oxopropyl)-3-methyl-5-[(2-methylpropan-2-yl)oxycarbonyl]-1H-pyrrol-2-yl]methyl]-3-methyl-1H-pyrrole-2-carboxylic acid
• CAS: 157528-35-3
• 化学式: C₂₃H₃₁ClN₂O₆
• 分子量: 466.962
• InChiKey: WNVGTMSHZMVQIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5'-(tert-butoxycarbonyl)-3-(2-chloroethyl)-4'-(2-methoxycarbonylethyl)-3',4-dimethyl-2,2'-dipyrrylmethane-5-carboxylic acid 在 potassium tert-butylate 、 zinc diacetate 、 对甲苯磺酸 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 叔丁醇 为溶剂， 反应 131.0h， 生成 8,13,17-tris(2-methoxycarbonylethyl)-2,7,12,18-tetramethyl-3-vinylporphyrin
  参考文献：
  名称：

  不依赖于氧的粪卟啉原 III 氧化酶 HemN 在粪卟啉原 III 向原卟啉原 IX 的转化过程中利用硬卟啉原作为反应中间体

  摘要：

  摘要 在血红素生物合成过程中，不依赖氧的粪卟啉原 III 氧化酶 HemN 催化粪卟啉原 III 的 A 环和 B 环上的两个丙酸侧链氧化脱羧为相应的乙烯基，生成原卟啉原 IX。在这里，研究了 HemN 催化过程中两个脱羧步骤的顺序。通过HPLC分析分离出具有HemN活性的反应中间体，并通过质谱法鉴定为单乙烯基三丙酸卟啉。这种单乙烯基反应中间体在 HPLC 分析过程中表现出与硬卟啉（3-乙烯基-8,13,17-三丙酸-2,7,12,18-四甲基卟啉）相同的色谱行为。此外，HemN 能够利用化学合成的硬卟啉原作为底物并将其转化为原卟啉原 IX。

  DOI：

  10.1515/bc.2010.006
• 作为产物：
  描述：

  benzyl 5-acetoxymethyl-4-(2-chloroethyl)-3-methylpyrrole-2-carboxylate 在 palladium on activated charcoal Montmorillonite clay K-10 、 氢气 、 三乙胺 作用下， 以 甲醇 、 氯仿 为溶剂， 25.0 ℃ 、303.37 kPa 条件下， 反应 38.0h， 生成 5'-(tert-butoxycarbonyl)-3-(2-chloroethyl)-4'-(2-methoxycarbonylethyl)-3',4-dimethyl-2,2'-dipyrrylmethane-5-carboxylic acid
  参考文献：
  名称：

  Normal and Abnormal Heme Biosynthesis. 1. Synthesis and Metabolism of Di- and Monocarboxylic Porphyrinogens Related to Coproporphyrinogen-III and Harderoporphyrinogen:  A Model for the Active Site of Coproporphyrinogen Oxidase

  摘要：

  Coproporphyrinogen oxidase (copro'gen oxidase), which catalyses the conversion of coproporphyrinogen-III via a monovinylic intermediate to protoporphyrinogen-IX, is one of the least well understood enzymes in the heme biosynthetic pathway. To develop a model for the substrate recognition and binding recognition for this enzyme, a series of substrate analogues were prepared with two alkyl substituents on positions 13 and 17 in place of the usual propionate residues. Although the required substrate probes are porphyrinogens (hexahydroporphyrins), the corresponding porphyrin methyl esters were initialy synthesized via a,c-biladiene intermediates. These were hydrolyzed and reduced with 3% sodium amalgam to give the unstable porphyrinogens needed for the biochemical investigations. These modified structures were metabolized by avian preparations of copro'gen oxidase to give monovinylic products, but the second propionate residue was not further metabolized. In three cases, the metabolites were isolated and further characterized by proton NMR spectroscopy and mass spectrometry. When methyl or ethyl groups were placed at the 13 and 17 positions, the resulting porphyrinogens were very good substrates (although the ethyl version, mesoporphyrinogen-VI, gave slightly better results), but when propyl units were introduced metabolism was significantly inhibited and the butyl-substituted structure was only slightly transformed after long incubation periods. These results suggest the presence of an active-site lipophobic region near the catalytic site for copro'gen oxidase. The observation that the related 3-vinyl- and 3-ethylporphyrinogens with 13,17-diethyl substituents were not substrates for this enzyme confirmed the need for a second propionate residue to hold the substrate in place at the catalytic site.

  DOI：

  10.1021/jo981473f

文献信息

• Normal and Abnormal Heme Biosynthesis. 6. Synthesis and Metabolism of a Series of Monovinylporphyrinogens Related to Harderoporphyrinogen. Further Insights into the Oxidative Decarboxylation of Porphyrinogen Substrates by Coproporphyrinogen Oxidase
  作者：Timothy D. Lash、Ukti N. Mani、Anna-Sigrid I. M. Keck、Marjorie A. Jones

  DOI：10.1021/jo100083t

  日期：2010.5.21

  A series of vinylporphyrinogens were prepared to probe the enzyme coproporphyrinogen oxidase (CPO). Six (2-chloroethyl)porphyrins were synthesized from a common dipyrrylmethane via a,c-biladiene intermediates in excellent yields. Subsequent dehydrohalogenation with DBU in refluxing DMF then gave the required vinylporphyrin methyl esters, including harderoporphyrin-I, harderoporphyrin-III, and isoharderoporphyrin

  制备了一系列乙烯基卟啉原，以探测酶原卟啉原氧化酶（CPO）。从常见的二吡咯甲烷经a，c合成六种（2-氯乙基）卟啉-biladiene中间体，产率极高。随后在回流的DMF中用DBU进行脱卤化氢，得到所需的乙烯基卟啉甲酯，包括硬卟啉-I，硬卟啉-III和异硬卟啉。将相应的卟啉原羧酸与含有CPO酶的鸡红细胞裂解液一起孵育，并分析产物。硬质卟啉原III的17-乙基类似物，而不是其13-乙基异构体，被证明是CPO的优良底物，符合该酶活性位点的拟议模型。另外，显示出硬卟啉原-VII，即协同原卟啉原-IV代谢中的单乙烯基中间体，是该酶的同样良好的底物。但是，异硬质卟啉原缺乏外围取代基的正确顺序，也是CPO的底物。此外，显示出硬质卟啉原的非天然I型异构体可被CPO作用，但在这种情况下，可观察到进一步的代谢，从而提供了前所未有的三乙烯基卟啉原产物。分离出相应的卟啉甲酯，并通过FAB MS和质子NMR光谱进行
• Normal and Abnormal Heme Biosynthesis. 1. Synthesis and Metabolism of Di- and Monocarboxylic Porphyrinogens Related to Coproporphyrinogen-III and Harderoporphyrinogen:  A Model for the Active Site of Coproporphyrinogen Oxidase
  作者：Timothy D. Lash、Ukti N. Mani、Martin A. Drinan、Chun Zhen、Troii Hall、Marjorie A. Jones

  DOI：10.1021/jo981473f

  日期：1999.1.1

  Coproporphyrinogen oxidase (copro'gen oxidase), which catalyses the conversion of coproporphyrinogen-III via a monovinylic intermediate to protoporphyrinogen-IX, is one of the least well understood enzymes in the heme biosynthetic pathway. To develop a model for the substrate recognition and binding recognition for this enzyme, a series of substrate analogues were prepared with two alkyl substituents on positions 13 and 17 in place of the usual propionate residues. Although the required substrate probes are porphyrinogens (hexahydroporphyrins), the corresponding porphyrin methyl esters were initialy synthesized via a,c-biladiene intermediates. These were hydrolyzed and reduced with 3% sodium amalgam to give the unstable porphyrinogens needed for the biochemical investigations. These modified structures were metabolized by avian preparations of copro'gen oxidase to give monovinylic products, but the second propionate residue was not further metabolized. In three cases, the metabolites were isolated and further characterized by proton NMR spectroscopy and mass spectrometry. When methyl or ethyl groups were placed at the 13 and 17 positions, the resulting porphyrinogens were very good substrates (although the ethyl version, mesoporphyrinogen-VI, gave slightly better results), but when propyl units were introduced metabolism was significantly inhibited and the butyl-substituted structure was only slightly transformed after long incubation periods. These results suggest the presence of an active-site lipophobic region near the catalytic site for copro'gen oxidase. The observation that the related 3-vinyl- and 3-ethylporphyrinogens with 13,17-diethyl substituents were not substrates for this enzyme confirmed the need for a second propionate residue to hold the substrate in place at the catalytic site.
• The oxygen-independent coproporphyrinogen III oxidase HemN utilizes harderoporphyrinogen as a reaction intermediate during conversion of coproporphyrinogen III to protoporphyrinogen IX
  作者：Katrin Rand、Claudia Noll、Hans Martin Schiebel、Dorit Kemken、Thomas Dülcks、Markus Kalesse、Dirk W. Heinz、Gunhild Layer

  DOI：10.1515/bc.2010.006

  日期：2010.1.1

  Abstract During heme biosynthesis the oxygen-independent coproporphyrinogen III oxidase HemN catalyzes the oxidative decarboxylation of the two propionate side chains on rings A and B of coproporphyrinogen III to the corresponding vinyl groups to yield protoporphyrinogen IX. Here, the sequence of the two decarboxylation steps during HemN catalysis was investigated. A reaction intermediate of HemN activity

  摘要 在血红素生物合成过程中，不依赖氧的粪卟啉原 III 氧化酶 HemN 催化粪卟啉原 III 的 A 环和 B 环上的两个丙酸侧链氧化脱羧为相应的乙烯基，生成原卟啉原 IX。在这里，研究了 HemN 催化过程中两个脱羧步骤的顺序。通过HPLC分析分离出具有HemN活性的反应中间体，并通过质谱法鉴定为单乙烯基三丙酸卟啉。这种单乙烯基反应中间体在 HPLC 分析过程中表现出与硬卟啉（3-乙烯基-8,13,17-三丙酸-2,7,12,18-四甲基卟啉）相同的色谱行为。此外，HemN 能够利用化学合成的硬卟啉原作为底物并将其转化为原卟啉原 IX。