5'-(tert-butoxycarbonyl)-3,4'-bis(2-methoxycarbonylethyl)-3',4-dimethyl-2,2'-dipyrrylmethane-5-carboxylic acid | 61565-25-1

• 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)-3,4'-bis(2-methoxycarbonylethyl)-3',4-dimethyl-2,2'-dipyrrylmethane-5-carboxylic acid
• 英文别名: 4-(3-methoxy-3-oxopropyl)-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: 61565-25-1
• 化学式: C₂₅H₃₄N₂O₈
• 分子量: 490.554
• InChiKey: XCCDWGOORNSURH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  35
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  148
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5'-(tert-butoxycarbonyl)-3,4'-bis(2-methoxycarbonylethyl)-3',4-dimethyl-2,2'-dipyrrylmethane-5-carboxylic acid 在 甲醇 、 硫酸 、 氢溴酸 、 三氟乙酸 、 copper dichloride 作用下， 反应 3.42h， 生成 3,8-bis(2-methoxycarbonylethyl)-2,7,12,18-tetramethyl-13,17-dipropylporphyrin
  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
• 作为产物：
  描述：

  5-(苄氧羰基)-2,4-二甲基-3-吡咯丙酸甲酯 在 氢气 、 对甲苯磺酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 5'-(tert-butoxycarbonyl)-3,4'-bis(2-methoxycarbonylethyl)-3',4-dimethyl-2,2'-dipyrrylmethane-5-carboxylic acid
  参考文献：
  名称：

  卟啉的合成和生物合成研究。第8部分。与尿卟啉I相关的七，六和五羧基卟啉的合成

  摘要：

  标题卟啉，作为卟啉生物合成中的异常代谢产物，已经通过费歇尔和b-氧杂环丁烷路线合成，并与天然物质进行了比较。酶学实验表明，尿卟啉原-I在体内和体外的转化都是非特异性的，并且通过两种中间的六羧酸卟啉原通过两种可能的途径发生。

  DOI：

  10.1039/p19870000277

文献信息

• Normal and abnormal heme biosynthesis. Part 7. Synthesis and metabolism of coproporphyrinogen-III analogues with acetate or butyrate side chains on rings C and D. Development of a modified model for the active site of coproporphyrinogen oxidase
  作者：Timothy D. Lash、Teresa R. Lamm、J. Andy Schaber、Wen-hsiang Chung、Eric K. Johnson、Marjorie A. Jones

  DOI：10.1016/j.bmc.2010.12.053

  日期：2011.2

  methyl esters were synthesized by first generating a,c-biladienes by reacting a dipyrrylmethane with pyrrole aldehydes in the presence of HBr. Cyclization with copper(II) chloride in DMF, followed by demetalation with 15% H2SO4–TFA and reesterification, gave the required porphyrins in excellent yields. Hydrolysis with 25% hydrochloric acid and reduction with sodium-amalgam gave novel diacetate and dibutyrate

  用与C和D吡咯亚基连接的乙酸酯或丁酸酯基制备了卟啉原III的类似物。相应的卟啉甲酯是通过在氢溴酸存在下使二吡咯基甲烷与吡咯醛反应生成α，c-胆二烯而合成的。在DMF中用氯化铜（II）环化，然后用15％H 2 SO 4 -TFA脱金属并再酯化，以极好的收率得到所需的卟啉。用25％盐酸水解并用汞齐钠还原，得到新颖的双乙酸盐和双丁酸盐卟啉原9。双乙酸酯9a将其与鸡红细胞溶血产物（CRH）一起孵育，但由于这些制剂中存在的两种酶的共同作用，给出了复杂的结果。尿卟啉原脱羧酶（URO-D）与原卟啉原氧化酶（CPO）的分离允许评估这两种酶对双乙酸酯底物的影响。卟啉原9A证明是CPO相对差的衬底相比于天然底物粪卟啉原-III，并且仅A环丙酸酯部分被加工成显著程度。用纯化的人重组CPO孵育9a可获得相似的结果。双乙酸酯9a也是URO-D的底物，在这种情况下，卟啉原单乙酸盐是主要产品；然而，第二乙酸酯单元的一些
• Normal and Abnormal Heme Biosynthesis. 3.¹ Synthesis and Metabolism of Tripropionate Analogues of Coproporphyrinogen-III:  Novel Probes for the Active Site of Coproporphyrinogen Oxidase
  作者：Timothy D. Lash、Troii Hall、Ukti N. Mani、Marjorie A. Jones

  DOI：10.1021/jo001697+

  日期：2001.6.1

  (copro'gen oxidase) catalyses the oxidative decarboxylation of two propionate side chains on coproporphyrinogen-III to produce protoporphyrinogen-IX. This process is very poorly understood at a molecular level, and copro'gen oxidase remains one of the least well-characterized enzymes in the heme biosynthetic pathway. To provide a rigorous test for a proposed model for substrate recognition and binding

  辅助原卟啉原氧化酶（copro'gen oxidase）催化副原卟啉原-III上两个丙酸酯侧链的氧化脱羧，生成原原卟啉原-IX。在分子水平上对这一过程了解甚少，并且copro'gen氧化酶仍然是血红素生物合成途径中特征最差的酶之一。为了对拟议的底物识别和结合酶模型进行严格测试，制备了copro'gen-III的两个三丙酸酯类似物，其中乙基取代了位置13或17上的一个常见的丙酸酯残基。探针是卟啉原（六氢卟啉），相应的卟啉甲酯最初是通过三y烯和α，c-胆二烯中间体合成的。将它们水解并用3％钠汞齐还原，以提供生化研究所需的不稳定卟啉原。禽配体copro'gen氧化酶将具有13-乙基部分的修饰结构代谢，得到单乙烯基产物，但是异构体17-乙基卟啉原产生了二乙烯基产物，尽管总转化率较差。这些结果有力地支持了拟定的模型在辅酶氧化酶活性位点的结合。
• Pandey, Ravindra K.; Rezzano, Irene N.; Smith, Kevin M., Journal of Chemical Research, Miniprint, 1987, # 8, p. 2171 - 2192
  作者：Pandey, Ravindra K.、Rezzano, Irene N.、Smith, Kevin M.

  DOI：——

  日期：——
• 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.
• Synthetic and biosynthetic studies of porphyrins. Part 8. Syntheses of hepta-, hexa-, and penta-carboxylic porphyrins related to uroporphyrin-I
  作者：Anthony H. Jackson、Damrus Supphayen

  DOI：10.1039/p19870000277

  日期：——

  The title porphyrins, of interest as abnormal metabolites in porphyrin biosynthesis, have been synthesized by the Fischer, and b-oxobilane routes, and compared with the naturally derived materials. Enzymic experiments have shown that the conversion of uroporphyrinogen-I into coproporphyrinogen-I both in vivo and in vitro is non-specific and occurs by both possible pathways via the two intermediate

  标题卟啉，作为卟啉生物合成中的异常代谢产物，已经通过费歇尔和b-氧杂环丁烷路线合成，并与天然物质进行了比较。酶学实验表明，尿卟啉原-I在体内和体外的转化都是非特异性的，并且通过两种中间的六羧酸卟啉原通过两种可能的途径发生。