4,5-dichloro-2-(2'-hydroxybenzoyl)pyrrole | 31161-51-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4,5-dichloro-2-(2'-hydroxybenzoyl)pyrrole
• 英文别名: monodeoxypyoluteorin；(4,5-dichloro-1H-pyrrol-2-yl)(2-hydroxyphenyl)methanone；(4,5-dichloro-pyrrol-2-yl)-(2-hydroxy-phenyl)-methanone；4,5-Dichloro-2-(2-hydroxybenzoyl)-1h-pyrrole；(4,5-dichloro-1H-pyrrol-2-yl)-(2-hydroxyphenyl)methanone
• CAS: 31161-51-0
• 化学式: C₁₁H₇Cl₂NO₂
• 分子量: 256.088
• InChiKey: IZFHIEMNQOKFKB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  53.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4,5-dichloro-2-(2'-hydroxybenzoyl)pyrrole 在 Streptomyces coelicolor M₅₁₂ marinopyrrole KY₂₈ 作用下， 生成 marinopyrrole A
  参考文献：
  名称：

  Flavoenzyme-Catalyzed Atropo-Selective N,C-Bipyrrole Homocoupling in Marinopyrrole Biosynthesis

  摘要：

  Axially chiral biaryl compounds are frequently encountered in nature where they exhibit diverse biological properties. Many are biphenols that have C-C or C-O linkages installed by cytochrome P450 oxygenases that control the regio- and stereoselectivity of the intermolecular coupling reaction. In contrast, bipyrrole-coupling enzymology has not been observed. Marinopyrroles, produced by a marine-derived streptomycete, are the first 1,3'-bipyrrole natural products. On the basis of marinopyrrole's unusual bipyrrole structure, we explored its atropo-selective biosynthesis in Streptomyces sp. CNQ-418 in order to elucidate the N,C-bipyrrole homocoupling enzymology. Through a series of genetic experiments involving the discovery and heterologous expression of marinopyrrole biosynthesis genes, we report that two flavin-dependent halogenases catalyze the unprecedented homocoupling reaction.

  DOI：

  10.1021/ja305670f
• 作为产物：
  描述：

  吡咯-2-羧酸乙酯 在 正丁基锂 、 磺酰氯 、 三溴化硼 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 4,5-dichloro-2-(2'-hydroxybenzoyl)pyrrole
  参考文献：
  名称：

  [EN] MCL-1 MODULATING COMPOSITIONS
  [FR] COMPOSITIONS DE MODULATION DE MCL-1

  摘要：

  本发明涉及海洋吡咯酮A衍生物和吡洛特霉素衍生物，以及治疗与Mcl-l误调节相关的疾病的方法，例如白血病、淋巴瘤、多发性骨髓瘤、黑色素瘤或胰腺癌。我们描述了一些示范性化合物，这些化合物可以包含在药物组合物中，并且它们可作为治疗剂单独使用或与其他抗癌治疗方法结合使用，例如抗Bcl-2剂。

  公开号：

  WO2013112878A1

文献信息

• Oxidative halogenation of substituted pyrroles with Cu(II). Part<b>IV.</b>Bromination of 2-(2′-hydroxybenzoyl)pyrrole. A new synthesis of bioactive analogs of monodeoxypyoluteorin
  作者：Salvatore Petruso、Silvana Bonanno、Sergio Caronna、Maurizio Ciofalo、Benedetta Maggio、Domenico Schillaci

  DOI：10.1002/jhet.5570310442

  日期：1994.7

  The selective bromination with copper(II) bromide of the pyrrole ring in 2-(2′-hydroxybenzoyl)pyrrole II in the heterogeneous phase is described giving in almost quantitative yield the 4,5-dibromo derivative VI. The subsequent introduction of halogen into the phenol moiety was observed when the reaction was performed in the homogeneous phase with an excess of halogenating agent. The pentabromo derivative

  描述了在异相中用2-（2'-羟基苯甲酰基）吡咯II中的吡咯环的溴化铜（II）选择性溴化，得到几乎定量的4,5-二溴衍生物VI。当在均相中与过量的卤化剂进行反应时，观察到随后将卤素引入酚部分。通过彻底溴化标题化合物，获得了对金黄色葡萄球菌非常有活性的化合物五溴衍生物IX（mic = 17 nmoles / dm -3）。II的氯代衍生物收率低 通过母体化合物与氯化铜（II）的反应获得。
• Antibacterial Marinopyrroles and Pseudilins Act as Protonophores
  作者：Gabriel Castro-Falcón、Jan Straetener、Jan Bornikoel、Daniela Reimer、Trevor N. Purdy、Anne Berscheid、Florence M. Schempp、Dennis Y. Liu、Roger G. Linington、Heike Brötz-Oesterhelt、Chambers C. Hughes

  DOI：10.1021/acschembio.3c00773

  日期：2024.3.15

  force (PMF) that is essential for cell viability. The compounds show potent protonophore activity but do not appear to destroy the integrity of the cytoplasmic membrane via the formation of larger pores or interfere with the stability of the peptidoglycan sacculus. Thus, our current model for the antibacterial MoA of marinopyrrole, pentachloropseudilin, and pentabromopseudilin stipulates that the acidic

  阐明抗菌天然产物的作用机制 （MoA） 对于评估其作为新型抗生素的潜力至关重要。马里诺吡咯、五氯杂二烯和五溴吡啶是密集卤化的杂化吡咯-苯酚天然产物，对金黄色葡萄球菌等革兰氏阳性细菌病原体具有强效活性。然而，它们发挥这种抗菌活性的确切方式尚未确定。在这项研究中，我们探讨了它们的构效关系，确定了它们在细菌细胞中的空间位置，并研究了它们的 MoA。我们表明，天然产物具有基于膜去极化和质子动力 （PMF） 耗散的共同 MoA，这对细胞活力至关重要。这些化合物显示出强大的原子细胞活性，但似乎不会通过形成更大的孔来破坏细胞质膜的完整性或干扰肽聚糖囊的稳定性。因此，我们目前的 marinopyrrole、pentachloropseudilin 和 pentabromopseudilin 的抗菌 MoA 模型规定酸性化合物插入细胞膜并在细胞内运输质子。该 MoA 可以解释已报道的这些化合物在哺乳动物细胞
• Structures, Reactivities, and Antibiotic Properties of the Marinopyrroles A−F
  作者：Chambers C. Hughes、Christopher A. Kauffman、Paul R. Jensen、William Fenical

  DOI：10.1021/jo1002054

  日期：2010.5.21

  Cultivation of actinomycete strain CNQ-418, retrieved from a deep ocean sediment sample off the coast of La Jolla, CA, has provided marinopyrroles A F. Sharing just 98% 16S rRNA gene sequence identity with S. sannurensis, the strain likely represents a new Streptomyces species. The metabolites contain an unusual 1,3'-bipyrrole core decorated with several chlorine and bromine substituents and possess marked antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The congested N,C-biaryl bond establishes an axis of chirality that, for marinopyrroles A-E, is configurationally stable at room temperature. Moreover, the natural products are fashioned strictly in the M-configuration. The Paal-Knorr condensation was adapted for the synthesis of the 1,3'-bipyrrole core. Halogenation of this material with N-bromosuccinimide cleanly furnished the 4,4',5,5'-tetrahalogenated core that characterizes this class of marine-derived metabolites.
• [EN] MCL-1 MODULATING COMPOSITIONS<br/>[FR] COMPOSITIONS DE MODULATION DE MCL-1
  申请人：PENN STATE RES FOUND

  公开号：WO2013112878A1

  公开（公告）日：2013-08-01

  The present invention relates to marinopyrrole A derivatives and pyoluteorin derivatives and methods of treatment of disorders associated with misregulation of Mcl-l, e.g., leukemia, lymphoma, multiple myeloma, melanoma, or pancreatic cancer. We describe exemplary compounds, which may be contained in pharmaceutical compositions, and their use as therapeutic agents either alone or in combination with other anti-cancer treatments, e.g., anti-Bcl- 2 agents.

  本发明涉及海洋吡咯酮A衍生物和吡洛特霉素衍生物，以及治疗与Mcl-l误调节相关的疾病的方法，例如白血病、淋巴瘤、多发性骨髓瘤、黑色素瘤或胰腺癌。我们描述了一些示范性化合物，这些化合物可以包含在药物组合物中，并且它们可作为治疗剂单独使用或与其他抗癌治疗方法结合使用，例如抗Bcl-2剂。
• Flavoenzyme-Catalyzed Atropo-Selective <i>N,C</i>-Bipyrrole Homocoupling in Marinopyrrole Biosynthesis
  作者：Kazuya Yamanaka、Katherine S. Ryan、Tobias A. M. Gulder、Chambers C. Hughes、Bradley S. Moore

  DOI：10.1021/ja305670f

  日期：2012.8.1

  Axially chiral biaryl compounds are frequently encountered in nature where they exhibit diverse biological properties. Many are biphenols that have C-C or C-O linkages installed by cytochrome P450 oxygenases that control the regio- and stereoselectivity of the intermolecular coupling reaction. In contrast, bipyrrole-coupling enzymology has not been observed. Marinopyrroles, produced by a marine-derived streptomycete, are the first 1,3'-bipyrrole natural products. On the basis of marinopyrrole's unusual bipyrrole structure, we explored its atropo-selective biosynthesis in Streptomyces sp. CNQ-418 in order to elucidate the N,C-bipyrrole homocoupling enzymology. Through a series of genetic experiments involving the discovery and heterologous expression of marinopyrrole biosynthesis genes, we report that two flavin-dependent halogenases catalyze the unprecedented homocoupling reaction.