5-[2,3,5,6-tetrafluoro-4-(2,2-dimethyl-1,3-dioxolan-4-yl-methoxy)]-dipyrromethane

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-[2,3,5,6-tetrafluoro-4-(2,2-dimethyl-1,3-dioxolan-4-yl-methoxy)]-dipyrromethane
• 英文别名: 5-[2,3,5,6-tetrafluoro-4-(2,2-dimethyl-1,3-dioxolan-4-yl-methoxy)phenyl]dipyrromethane；2-[[4-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]-2,3,5,6-tetrafluorophenyl]-(1H-pyrrol-2-yl)methyl]-1H-pyrrole
• 化学式: C₂₁H₂₀F₄N₂O₃
• 分子量: 424.395
• InChiKey: SCYBSQKGLPRJET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  59.3
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-[2,3,5,6-tetrafluoro-4-(2,2-dimethyl-1,3-dioxolan-4-yl-methoxy)]-dipyrromethane 在 三氟化硼乙醚 、 N,N-二异丙基乙胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以31%的产率得到8-[4-(2,3-dihydroxy-propyl-1-oxy)-2,3,5,6-tetrafluorophenyl]-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  参考文献：
  名称：

  Nucleophilic Substitution on (Pentafluorophenyl)dipyrromethane: A New Route to Building Blocks for Functionalized BODIPYs and Tetrapyrroles

  摘要：

  The reaction of alcohols with (pentafluorophenyl)dipyrromethane (PFP-DPM) under basic conditions has been studied, giving access to the corresponding alkoxy-substituted DPMs. This method represents the first high-yielding substitution of PFP-DPM carried out with oxygen nucleophiles. Condensation of these prefunctionalized DPMs with aldehydes led to the respective trans-A(2)B(2) porphyrins. This pathway allows a simple synthesis of multifunctionalized tetrapyrroles. Oxidation and boron complexation of these DPMs, on the other hand, led to meso-functionalized difluoroboraindacenes (BODIPYs). In addition, nucleophilic substitution of PFP-BODIPY with sodium azide led to a 4-azidophenyl derivative, thus further enhancing the scope of reactive sites suitable for subsequent transformations.

  DOI：

  10.1021/acs.orglett.5b00082
• 作为产物：
  描述：

  五氟苯甲醛 在 三氟乙酸 、 potassium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 24.58h， 生成 5-[2,3,5,6-tetrafluoro-4-(2,2-dimethyl-1,3-dioxolan-4-yl-methoxy)]-dipyrromethane
  参考文献：
  名称：

  Nucleophilic Substitution on (Pentafluorophenyl)dipyrromethane: A New Route to Building Blocks for Functionalized BODIPYs and Tetrapyrroles

  摘要：

  The reaction of alcohols with (pentafluorophenyl)dipyrromethane (PFP-DPM) under basic conditions has been studied, giving access to the corresponding alkoxy-substituted DPMs. This method represents the first high-yielding substitution of PFP-DPM carried out with oxygen nucleophiles. Condensation of these prefunctionalized DPMs with aldehydes led to the respective trans-A(2)B(2) porphyrins. This pathway allows a simple synthesis of multifunctionalized tetrapyrroles. Oxidation and boron complexation of these DPMs, on the other hand, led to meso-functionalized difluoroboraindacenes (BODIPYs). In addition, nucleophilic substitution of PFP-BODIPY with sodium azide led to a 4-azidophenyl derivative, thus further enhancing the scope of reactive sites suitable for subsequent transformations.

  DOI：

  10.1021/acs.orglett.5b00082

文献信息

• [EN] SPECIFICALLY MESO-SUBSTITUTED PORPHYRINS AND CHLORINS FOR PHOTODYNAMIC THERAPY<br/>[FR] PORPHYRINES ET CHLORES MÉSO-SUBSTITUÉS DE FAÇON SPÉCIFIQUE POUR LA THÉRAPIE PHOTODYNAMIQUE
  申请人：BIOLITEC UNTERNEHMENSBETEILIGUNGS II AG

  公开号：WO2016051361A1

  公开（公告）日：2016-04-07

  Biologically active compounds that can be used as photosensitizers for diagnostic and therapeutic applications, particularly for PDT of cancer, infections and other hyperproliferative diseases, fluorescence diagnosis and PDT treatment of a non-tumorous indication such as arthritis, inflammatory diseases, viral or bacterial infections, dermatological, opthamological or urological disorders are provided as well as providing methods to obtain them in pharmaceutical quality. One embodiment consists of a method to synthesize a porphyrin with a defined arrangement of meso-substituents and then converting this porphyrin system to a chlorin system by dihydroxylation or reduction, and if more than one isomer is formed separate them by chromatography either on normal or reversed phase silica. In another embodiment the substituents on the porphyrin are selected to direct the reduction or dihydroxylation to the chlorin so that a certain isomer is selectively formed. Another embodiment is to provide amphiphilic compounds with a higher membrane affinity and increased PDT-efficacy. In other embodiments the nucleophilic substitution on pentafluorophenyl-substituted tetrapyrroles is used to obtain compounds with a high PDT-efficacy. In another embodiment substituents are identified that via their steric and/or electronic influence direct the dihydroxylation or reduction with diimine so that one isomer is favored. Another embodiment consists of formulating the desired tetrapyrrole photosensitizer into a pharmaceutical formulation to be injected into the body avoiding undesirable effects like solubility problems or delayed pharmacokinetics of the tetrapyrrole systems.

  提供可用作诊断和治疗应用的光敏化合物，特别是用于光动力疗法治疗癌症、感染和其他高增殖性疾病，以及用于非肿瘤指示如关节炎、炎症性疾病、病毒或细菌感染、皮肤病、眼科或泌尿系统疾病的荧光诊断和光动力疗法治疗，同时提供获得这些化合物的制药质量的方法。一个实施例包括一种合成具有定义的间位取代基排列的卟啉的方法，然后通过二羟基化或还原将该卟啉系统转化为氯卟啉系统，并且如果形成多个异构体，则通过在正相或反相硅胶上进行色谱分离它们。在另一个实施例中，选择卟啉上的取代基以将还原或二羟基化定向到氯卟啉，从而选择性地形成某个异构体。另一个实施例是提供具有更高膜亲和力和增加的光动力疗效的两性化合物。在其他实施例中，利用对五氟苯基取代的四吡咯烯的亲核取代来获得具有高光动力疗效的化合物。在另一个实施例中，确定通过它们的立体和/或电子影响引导二羟基化或二亚胺还原的取代基，以便偏好某个异构体。另一个实施例包括将所需的四吡咯光敏化合物配制成药物制剂，注射到体内，避免不良影响，如溶解度问题或四吡咯系统的延迟药代动力学。
• Nucleophilic Substitution on (Pentafluorophenyl)dipyrromethane: A New Route to Building Blocks for Functionalized BODIPYs and Tetrapyrroles
  作者：Hartwig R. A. Golf、Hans-Ulrich Reissig、Arno Wiehe

  DOI：10.1021/acs.orglett.5b00082

  日期：2015.2.20

  The reaction of alcohols with (pentafluorophenyl)dipyrromethane (PFP-DPM) under basic conditions has been studied, giving access to the corresponding alkoxy-substituted DPMs. This method represents the first high-yielding substitution of PFP-DPM carried out with oxygen nucleophiles. Condensation of these prefunctionalized DPMs with aldehydes led to the respective trans-A(2)B(2) porphyrins. This pathway allows a simple synthesis of multifunctionalized tetrapyrroles. Oxidation and boron complexation of these DPMs, on the other hand, led to meso-functionalized difluoroboraindacenes (BODIPYs). In addition, nucleophilic substitution of PFP-BODIPY with sodium azide led to a 4-azidophenyl derivative, thus further enhancing the scope of reactive sites suitable for subsequent transformations.