5,10,15,20-tetra(n-hexyl)phorphyrin | 54976-01-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四吡咯及其衍生物
• 英文名称: 5,10,15,20-tetra(n-hexyl)phorphyrin
• 英文别名: 5,10,15,20-tetrahexylporphyrin；meso-tetrahexylporphyrin；5,10,15,20-tetrahexyl-porphyrin；5,10,15,20-tetrahexyl-21H,23H-porphine；Tetrahexylporphin
• CAS: 54976-01-1
• 化学式: C₄₄H₆₂N₄
• 分子量: 647.003
• InChiKey: GCSXDWFGECKCBR-NKNGOTKRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  13.15
• 重原子数：
  48.0
• 可旋转键数：
  20.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  57.36
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  5,10,15,20-tetra(n-hexyl)phorphyrin 在 四氧化锇 、 sodium hydrogensulfite 作用下， 以 吡啶 、 二氯甲烷 、 甲醇 、 水 为溶剂， 反应 24.0h， 以65%的产率得到5,10,15,20-tetrahexyl-7,8-dihydroxy-7,8-chlorin
  参考文献：
  名称：

  Application of β-functionalized dihydroxy-chlorins for PDT

  摘要：

  本发明提供了可用作诊断和治疗应用的光敏剂的生物活性化合物，特别是用于癌症、感染和其他过度增殖疾病的光动力治疗、荧光诊断以及非肿瘤指示如关节炎、炎症性疾病、病毒或细菌感染、皮肤、眼科或泌尿系统疾病的PDT治疗。这些化合物属于β-功能化的羟基和双羟基氯菁类，具有通用公式。

  公开号：

  US09156849B2
• 作为产物：
  描述：

  C₄₄H₆₈N₄ 在 四氯苯醌 作用下， 反应 1.0h， 生成 5,10,15,20-tetra(n-hexyl)phorphyrin
  参考文献：
  名称：

  蒙脱石K10和3Å分子筛可实现高收率制备的中四烷基卟啉的纳米级成像

  摘要：

  我们已经开发了一种高产合成的内消旋-tetraalkylporphyrins，这在以前已经获得只有较低的产率。通过使用蒙脱石K10作为酸催化剂和3Å分子筛作为脱水剂，使用某些脂肪族醛可以达到70％的收率。具有癸基（C10）或更长链的游离碱卟啉在溶剂/表面界面以单分子水平成像。高取向热解石墨（HOPG）被用作π堆积表面，而1-苯基辛烷和1-苯基壬烷被用作溶剂。从C13到C16观察到奇偶效应。对于C13 单晶X射线结构使人们能够以前所未有的方式洞悉二维包装如何扩展为三维晶格。

  DOI：

  10.1002/chem.201300532

文献信息

• APPLICATION OF BETA-FUNCTIONALIZED DIHYDROXY-CHLORINS FOR PDT
  申请人：Aicher Daniel

  公开号：US20130041307A1

  公开（公告）日：2013-02-14

  The present invention provides methods to obtain 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, ophthalmological or urological disorders. An embodiment of the present invention consists of a method to synthesize diketo-chlorins as precursors. In yet another embodiment these precursors are converted to β-functionalized hydroxy- and dihydroxy-chlorins. Another embodiment is to provide amphiphilic compounds with a higher membrane affinity and increased PDT-efficacy. Another embodiment consists of the formulation of the desired isomer into a liposomal formulation to be injected avoiding undesirable effects like precipitation at the injection site or delayed pharmacokinetics of the tetrapyrrole systems.

  本发明提供了一种获得生物活性化合物的方法，这些化合物可以用作诊断和治疗应用的光敏剂，特别是用于癌症、感染和其他过度增殖性疾病的光动力疗法（PDT），荧光诊断和非肿瘤指示物（如关节炎、炎症性疾病、病毒或细菌感染、皮肤病、眼科疾病或泌尿系统疾病）的PDT治疗。本发明的一种实施例包括合成二酮-叶绿素作为前体的方法。在另一种实施例中，这些前体被转化为β-官能化的羟基和二羟基-叶绿素。另一种实施例是提供具有更高膜亲和力和增加PDT效果的两性化合物。另一种实施例包括将所需的异构体制成脂质体制剂以注射，避免不良影响，如在注射部位沉淀或四吡咯系统的延迟药代动力学。
• METHOD AND APPLICATION OF UNSYMMETRICALLY meso-SUBSTITUTED PORPHYRINS AND CHLORINS FOR PDT
  申请人：Wiehe Arno

  公开号：US20110206613A1

  公开（公告）日：2011-08-25

  Biologically active compounds are provided 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, ophthalmological or urological disorders 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 another embodiment a method to reductively cleave the osmate(VI)ester avoiding the use of gaseous H 2 S is provided. 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 formulate the desired isomer into a liposomal formulation to be injected avoiding undesirable effects like solubility problems or delayed pharmacokinetics of the tetrapyrrole systems.

  提供了生物活性化合物，可用作诊断和治疗应用的光敏剂，特别是用于癌症、感染和其他增生性疾病的光动力疗法、荧光诊断和非肿瘤指示的光动力治疗，如关节炎、炎症性疾病、病毒或细菌感染、皮肤病、眼科疾病或泌尿系统疾病，同时提供获得它们的制药质量的方法。其中一种实施方式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林系统，并在形成多个异构体时通过色谱法在正相或反相硅胶上将它们分离。在另一种实施方式中，选择卟啉上的取代基以将还原或二羟基化引导到氯林，从而选择性地形成某个异构体。另一种实施方式是提供具有更高膜亲和力和增强光动力治疗效果的两性化合物。在另一种实施方式中，提供了一种还原性剖离酸酯的方法，避免使用气态H2S。在另一种实施方式中，通过识别取代基，通过它们的立体和/或电子影响，将二羟基化或二亚胺还原引导到偏爱的一个异构体。另一种实施方式包括将所需的异构体配制成脂质体制剂以注射，避免不良影响，如溶解度问题或类四吡咯系统的延迟药代动力学。
• Unique 1∶2 adduct formation of meso-tetraarylporphyrins and meso-tetraalkylporphyrins with BF₃: a spectroscopic and ab initio study
  作者：Daryoush Mohajer、Saeed Zakavi、Saeed Rayati、Mansour Zahedi、Nasser Safari、Hamid Reza Khavasi、Shant Shahbazian

  DOI：10.1039/b407529c

  日期：——

  The interaction of a series of free base meso-tetraarylporphyrins (arylpor) and meso-tetraalkylporphyrins (alkylpor) with BF3·Et2O, with different molar ratios (<1∶1 to >1∶2) in chloroform, immediately and exclusively yielded the 1∶2 adducts (BF3)2por. The close spectral correlation between the corresponding (BF3)2por and (CF3COOH)2por were suggestive of similar saddled porphyrin core structures with BF3 molecules coordinated to the two pyrrolenine nitrogen donors, and simultaneously hydrogen bonded to the pyrrole NH groups of the porphyrin macrocycle from above and below the plane of the porphyrins. The complexation of various arylpor and alkylpor with BF3 and their protonation with CF3COOH caused red shifts of the Soret bands (3 to ∼30 nm). The interaction of arylpor (except H2tmp) and also H2t(tert-Bu)p with BF3·OEt2 and CF3COOH demonstrated red shifts of the Q(0,0) bands (5.4 to 40 nm). In contrast, reactions of the alkylpor (alkyl = Me, Et, n-Pr, n-Bu) and H2tmp with BF3 or CF3COOH displayed blue shifts of the Q(0,0) bands (−13.5 to −31.8 nm). The observed differences in the Q(0,0) bands shifts for the complexation of arylpor versus alkylpor are presumably related to the relative co-planarity of the meso-aryl groups with the porphyrin core, and the possible π-interactions in the former. It is noteworthy that while the UV-vis spectrum of H4t(tert-Bu)p2+ was very sensitive to excess amounts of CF3COOH, the UV-vis spectrum of (BF3)2H2t(tert-Bu)p showed no changes in the presence of additional BF3·Et2O. The 1H and 13C NMR spectra of the 1∶2 adducts demonstrated a general correspondence with those of the related protonated porphyrins. However, the pyrrole NH signals of the (BF3)2por were upfield shifted to an unusual extent as compared to those of the diprotonated H2por2+ species. This effect presumably is due to the weaker NH hydrogen bonding of the 1∶2 molecular complexes compared to the protonated porphyrins. It was also observed that, in contrast to the gradual upfield shifts of the NH signals of H2por2+ with increasing CF3COOH concentration, the NH signals of (BF3)2por complexes remained fixed and independent of BF3·OEt2 concentration. 19F and 11B NMR spectra of various (BF3)2por showed upfield shifts of both 11B and 19F signals relative to those of BF3·OEt2. The observed larger upfield shifts of 11B (−6.48 to −6.71 ppm) signals than those of 19F (−3.53 to −4.20 ppm), apparently reflect direct coordination of the B atoms to the nitrogen donors and their closer proximity to the porphyrin core. The results of ab initio calculations illustrated that in (BF3)2H2tpp the two BF3 molecules are coordinated to the pyrrolenine nitrogen donors and are hydrogen-bonded to the pyrrole NH groups. Also calculations indicated that the addition of a BF3 molecule to the 1∶1 species, BF3H2tpp, is more favorable (2.4 kcal mol−1) than its coordination to H2tpp, and the 1∶2 molecular complex is more stable (14.5 kcal mol−1) than the 1∶1 adduct. A mechanism is proposed to explain the absence of the 1∶1 adduct and the observed symmetric NMR spectra of the pyrrole rings and fluorines in (BF3)2por.

  一系列游离基中四芳基卟啉（芳基卟啉）和中四烷基卟啉（烷基卟啉）与氯仿中不同摩尔比（<1â¶1 到 >1â¶2）的 BF3Â-Et2O 相互作用，立即生成了 1â¶2加合物 ( )2por。相应的 ( )2por 和 (CF3COOH)2por 之间的光谱密切相关，这表明 分子与两个吡咯啉氮供体配位，同时从卟啉平面的上方和下方与卟啉大环的吡咯 NH 基团氢键结合，形成了类似的鞍状卟啉核心结构。各种芳基卟啉和烷基卟啉与 的络合以及它们与 CF3COOH 的质子化作用会导致索雷特谱带发生红移（3 至 §30 nm）。芳基硼（H2tmp 除外）和 H2t(tert-Bu)p 与 Â-OEt2 和 CF3COOH 的相互作用导致 Q(0,0) 带发生红移（5.4 至 40 纳米）。相反，烷基por（烷基=Me、Et、n-Pr、n-Bu）和H2tmp与 或CF3COOH的反应则显示出Q（0,0）带的蓝移（§13.5至§31.8纳米）。所观察到的芳基卟啉与烷基卟啉络合时 Q(0,0) 带移动的差异可能与介芳基与卟啉核的相对共平面性以及前者中可能存在的 Ï 相互作用有关。值得注意的是，H4t(tert-Bu)p2+ 的紫外-可见光谱对过量的 CF3COOH 非常敏感，而 ( )2H2t(tert-Bu)p 的紫外-可见光谱在有额外的 Â-Et2O 存在时没有变化。1.2 加合物的 1H 和 13C NMR 光谱与相关质子化卟啉的 1H 和 13C NMR 光谱基本一致。然而，与二质子化的 H2por2+ 物种相比，( )2por 的吡咯 NH 信号发生了异常的上场偏移。这种效应可能是由于与质子化卟啉相比，1â¶2 分子复合物的 NH 氢键较弱。还观察到，随着 CF3COOH 浓度的增加，H2por2+ 的 NH 信号逐渐上移，与此相反，( )2por 复合物的 NH 信号保持固定，与 -OEt2 浓度无关。各种 ( )2por 的 19F 和 11B NMR 光谱显示，相对于 Â-OEt2 信号，11B 和 19F 信号都发生了上场移动。与 19F 信号（3.53 至 4.20 ppm）相比，观察到的 11B 信号（6.48 至 6.71 ppm）的上场移位更大，这显然反映了 B 原子与氮供体的直接配位以及它们与卟啉核心的距离更近。ab initio 计算的结果表明，在 ( )2H2tpp 中，两个 分子与吡咯啉氮供体配位，并与吡咯 NH 基团氢键结合。计算还表明，一个 分子与 1â¶1物种 H2tpp 的加成（2.4 kcal molâ1）比它与 H2tpp 的配位更有利，而且 1â¶2分子复合物比 1â¶1加合物更稳定（14.5 kcal molâ1）。本文提出了一种机制，以解释 ( )2por 中不存在 1â¶1 加合物以及所观察到的吡咯环和氟的对称核磁共振光谱。
• Effects of aldehyde or dipyrromethane substituents on the reaction course leading to meso-substituted porphyrins
  作者：G. Richard Geier、Jonathan S. Lindsey

  DOI：10.1016/j.tet.2004.09.081

  日期：2004.12

  To better understand the effects of diverse substituents on reactions leading to porphyrins, pyrrole + aldehyde condensations and related reactions of dipyrromethanes were examined. The course of pyrrole + aldehyde condensations was investigated by monitoring the yield of porphyrin (by UV-Vis spectroscopy), reaction of aldehyde (by TLC), and changes in the composition of oligomers (by laser desorption mass spectrometry). Reaction reversibility was examined via exchange experiments. Reversibility of reactions leading to porphyrin was further probed with studies of dipyrromethanes. The reaction course was found to depend on the nature of the substituent and the acid catalyst. Alkyl or electron-donating substituents displayed levels of reversibility (exchange/scrambling) on par or greater than that of the pbenyl substituent, whereas electron-withdrawing or sterically bulky substituents exhibited little to no reversibility. The results obtained provide insight into the electronic and steric effects of different substituents and should facilitate the design of synthetic plans for preparing porphyrinic macrocycles. (C) 2004 Elsevier Ltd. All rights reserved.
• Lead structures for applications in photodynamic therapy. Part 1: Synthesis and variation of m-THPC (Temoporfin) related amphiphilic A2BC-type porphyrins
  作者：Arno Wiehe、Yasser M. Shaker、Johan C. Brandt、Stefan Mebs、Mathias O. Senge

  DOI：10.1016/j.tet.2005.03.086

  日期：2005.6

  Photodynamic therapy (PDT) is a developing modality for the treatment of certain tumorous and other diseases. Considerable progress has been made in recent years in the search for new photosensitizers, in particular elucidating the role of localization of the photosensitizer. Known successful photosensitizers of the tetrapyrrole type are amphiphilic molecules, preferably localizing in cellular membrane structures. Thus, the quest for new photosensitizers requires the synthesis of unsymmetrically Substituted (amphiphilic) tetrapyrroles. In this article. we describe strategies for the de novo synthesis of amphiphilic tetrapyrroles using a 3-hydroxyphenyl substituted tetrapyrrolic system (Temoporfin) as the lead structure. From an applied science-oriented approach, such a set of amphiphilic porphyrins is best synthesized by combining well-developed condensation methods with subsequent functionalization via organolithium compound or transition metal catalyzed coupling protocols. Starting from simple A(2)- or AB-porphyrins, the synthesis of A(2)B-, A(3)-, A(3)B-, and A(2)BC-porphyrins with a mixed hydrophilic/hydrophobic substitution pattern is described. Because of the versatility of this approach to unsymmetrically Substituted porphyrins it is also applicable to other areas where porphyryns with a tailor-made substitution patterns are needed. for example. catalysts or molecular electronic devices based on tetrapyrroles. (c) 2005 Elsevier Ltd. All rights reserved.