(2S)-2-[(2,3-二羟基苯甲酰)氨基]-3-羟基-丙酸 | 7724-78-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (2S)-2-[(2,3-二羟基苯甲酰)氨基]-3-羟基-丙酸
• 英文名称: 2,3-dihydroxybenzoyl-L-serine
• 英文别名: enterobactin monomer；DHBA-L-Ser；N-(2,3-dihydroxybenzoyl)-L-serine；(2S)-2-[(2,3-dihydroxybenzoyl)amino]-3-hydroxypropanoic acid
• CAS: 7724-78-9
• 化学式: C₁₀H₁₁NO₆
• 分子量: 241.2
• InChiKey: VDTYHTVHFIIEIL-LURJTMIESA-N

物化性质

• 沸点：
  553.5±50.0 °C(Predicted)
• 密度：
  1.585±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  127
• 氢给体数：
  5
• 氢受体数：
  6

安全信息

• 海关编码：
  2924299090

反应信息

• 作为产物：
  描述：

  凝乳酶 在 水 作用下， 以 aq. buffer 为溶剂， 反应 1.5h， 生成 (2S)-2-[(2,3-二羟基苯甲酰)氨基]-3-羟基-丙酸
  参考文献：
  名称：

  Esterase-Catalyzed Siderophore Hydrolysis Activates an Enterobactin–Ciprofloxacin Conjugate and Confers Targeted Antibacterial Activity

  摘要：

  Enteric Gram-negative bacteria, including Escherichia coli, biosynthesize and deploy the triscatecholate siderophore enterobactin (Ent) in the vertebrate host to acquire iron, an essential nutrient. We report that Ent-Cipro, a synthetic siderophore-antibiotic conjugate based on the native Ent platform that harbors an alkyl linker at one of the catechols with a ciprofloxacin cargo attached, affords targeted antibacterial activity against E. coli strains that express the pathogen-associated iroA gene duster. Attachment of the siderophore to ciprofloxacin, a DNA gyrase inhibitor and broad-spectrum antibiotic that is used to treat infections caused by E. coli, generates an inactive prodrug and guides the antibiotic into the cytoplasm of bacteria that express the Ent uptake machinery (FepABCDG). Intracellular hydrolysis of the siderophore restores the activity of the antibiotic. Remarkably, Fes, the cytoplasmic Ent hydrolase expressed by all E. coli, does not contribute to Ent-Cipro activation. Instead, this processing step requires IroD, a cytoplasmic hydrolase that is expressed only by E. coli that harbor the iroA gene duster and are predominantly pathogenic. In the uropathogenic E. coli UTI89 and CFT073, Ent-Cipro provides antibacterial activity comparable to unmodified ciprofloxacin. This work highlights the potential of leveraging and targeting pathogen-associated microbial enzymes in narrow-spectrum antibacterial approaches. Moreover, because E. coli include harmless gut commensals as well as resident microbes that can contribute to disease, Ent-Cipro may provide a valuable chemical tool for strain-selective modulation of the microbiota.

  DOI：

  10.1021/jacs.8b01042

文献信息

• [EN] ANTIBACTERIAL SIDEROMYCINS<br/>[FR] SIDÉROMYCINES ANTIBACTÉRIENNES
  申请人：MILLER MARVIN J

  公开号：WO2016027262A1

  公开（公告）日：2016-02-25

  A compound, comprising: an Fe(III)-binding and/or Fe(III)-bound siderophore; one or more optional linker covalently bound to the siderophore; and daptomycin covalently bound to the linker, or, if no linker is present, then to the siderophore; or pharmaceutically acceptable salt or solvate thereof.

  一种化合物，包括：与Fe(III)结合和/或Fe(III)结合的铁载体；一个或多个可选的与铁载体共价结合的连接剂；以及共价结合到连接剂的达托霉素，或者如果没有连接剂存在，则共价结合到铁载体；或其药用可接受的盐或溶剂。
• [EN] CYCLIC PEROXIDES AS PRODRUGS FOR SELECTIVE DELIVERY OF AGENTS<br/>[FR] PEROXYDES CYCLIQUES UTILISÉS EN TANT QUE PROMÉDICAMENTS POUR L'ADMINISTRATION SÉLECTIVE D'AGENTS
  申请人：UNIV CALIFORNIA

  公开号：WO2015123595A1

  公开（公告）日：2015-08-20

  Disclosed herein, inter alia, are prodrug compositions and methods of using the same for treatment and detection of disease. Specifically, disclosed herein is a compound of formula (I) having spiro-fused 1,2,4-trioxolane and piperidine rings, namely, 1,2,4-trioxa- 8-azaspiro[4.5] decane. Also disclosed is a pharmaceutical composition containing the compound and a phannaceutically acceptable carrier.

  本文披露了前药组合物及其用于治疗和检测疾病的方法。具体地，本文披露了一种具有螺合1,2,4-三噁烷和哌啶环的化合物的公式(I)，即1,2,4-三氧杂-8-氮杂螺[4.5]癸烷。还披露了含有该化合物和药用载体的药物组合物。
• Synthesis and biological activity of analogues of vanchrobactin, a siderophore from Vibrio anguillarum serotype O2
  作者：Raquel G. Soengas、Marta Larrosa、Miguel Balado、Jaime Rodríguez、Manuel L. Lemos、Carlos Jiménez

  DOI：10.1039/b719713f

  日期：——

  Several analogues of vanchrobactin, a catechol siderophore isolated from the bacterial fish pathogen Vibrio anguillarum serotype O2 strain RV22, have been synthesized. The biological evaluation of these novel compounds showed that most of them are active as siderophores, as determined by growth promotion assays using the producer strain, as well as V. anguillarum serotype O1, Salmonella enterica, and Erwinia

  已经合成了vanchrobactin的几种类似物，vanchorobactin是一种从细菌鱼病原体鳗弧菌血清型O2菌株RV22中分离出的邻苯二酚铁载体。这些新型化合物的生物学评估表明，通过使用生产菌株以及鳗弧菌血清型O1，沙门氏菌和菊花欧文氏菌的生长促进测定法确定，它们中的大多数都具有铁载体的活性。这些化合物还给出了阳性的铬天青S（CAS）测试。基于这些结果，我们能够推断出一些构效关系。此外，我们发现了具有铁载体活性的类似物，该类似物具有适当的功能（氨基），可用作“特洛伊木马策略”中使用的抗生素载体。
• [DE] SIDEROPHOR-ANTIBIOTIKAKONJUGATE MIT 4- ODER 6-ZÄHNIGEN EISENCHELATOREN AUF DER BASIS VON AMINOSÄUREN ODER PEPTIDEN, VERFAHREN ZU IHRER HERSTELLUNG UND IHRE ANWENDUNG<br/>[EN] SIDEROPHORE ANTIBIOTIC CONJUGATES WITH TETRA- OR HEXADENTATE IRON CHELATORS ON THE BASIS OF AMINO ACIDS OR PEPTIDES, METHOD FOR PRODUCING THEM AND THE USE THEREOF<br/>[FR] CONJUGUES ANTIBIOTIQUES-SIDEROPHORES, AVEC CHELATEURS DU FER A 4 OU 6 DENTS, A BASE D'ACIDES AMINES OU DE PEPTIDES ; PROCEDES DE PRODUCTION ET UTILISATIONS ASSOCIES
  申请人：GRUENENTHAL GMBH

  公开号：WO2002070017A1

  公开（公告）日：2002-09-12

  Die Erfindung betrifft neue Konjugate von ß-Laktamantibiotika der allgemeinen Formel I mit 4- oder 6-zähnigen Eisenchelatoren oder deren acylierte Derivate als Siderophorkomponenten, abgeleitet von Aminosäuren bzw. Peptiden, wobei mindestens (2) Catecholsubstituenten beteiligt sind. Die Verbindungen können auf Grund ihrer Siderophorkomponenten über Eisentransportwege in Bakterienzellen eingeschleust werden und somit deren Wirksamkeit weitaus stärker verbessern bzw. erweitern, als bisherige Verbindungen dieser Art. Dadurch können bei nicht therapierbaren Problemkeimen Resistenzen überwunden werden. worin R1 = ein ß-Laktamantibiotikum, gegebenenfalls mit einer eingeschobenen weiteren Aminosäureeinheit, oder R1 = verschiedene Reste, die eine Catechol- oder Hydroxamatgruppe zur Ergänzung auf eine 6-zähnige Chelatorstruktur, gegebenenfalls in acylierter Form oder zusammen mit Spacergruppen und außerdem den Rest eines ß-Laktamantibiotikums, insbesondere eines Penicillin- oder Cephalosporinderivates, speziell Ampicillin, Amoxicillin oder Cefaclor, (als freie Säuren, in Form ihrer Salze oder ihrer leicht spaltbaren Ester) enthalten.

  本发明涉及一般式I的ß-内酰胺类抗生素与含有氨基酸或肽衍生物的4或6齿铁螯合物或其酰化衍生物作为铁载体组分的新共轭物，其中至少有(2)个邻二酚基团参与。由于这些化合物可以通过铁转运途径进入细菌细胞，因此可以比此类先前的化合物更大程度地提高或扩展其功效。因此，可以克服治疗难以治愈的问题菌株的耐药性。其中R1 = ß-内酰胺类抗生素，可能带有插入的其他氨基酸单元，或R1 = 包含邻二酚基团或羟肟基以补充6齿螯合物结构的不同基团，可能是酰化形式或与间隔基团一起，并且还包括ß-内酰胺类抗生素的余下部分，特别是青霉素或头孢菌素衍生物，特别是氨苄青霉素、阿莫西林或头孢克洛，(作为自由酸、其盐或易于分解的酯的形式)。
• Siderophore conjugates of photoactive dyes for photodynamic therapy
  申请人：CeramOptec Industries, Inc.

  公开号：US20040186087A1

  公开（公告）日：2004-09-23

  Siderophore-photosensitizer conjugates, their synthesis and use in photodynamic antimicrobial therapy (PACT) is disclosed. The advantage of this method is improvement of photodynamic antimicrobial therapy against, for example, pathogenic micro-organisms such as bacteria and fungi. Naturally occurring and synthetically available siderophore structures are conjugated chemically with photoactive compounds such as Chlorin e 6 to improve their penetration into bacterial cells and to increase antibacterial efficacy of photosensitizers via microbial proteins that recognize and transport iron-loaded siderophores. In this way, photosensitizers can be transported inside bacteria that otherwise could not cross the cell wall and membranes. Photodynamic activation of photosensitizers inside the cells of pathogenic microbes enables a more effective inhibition of cellular functions than application at the outer side of the cells. The siderophore-transporting systems of microbes are known to be specific for bacteria and fungi. Consequently, siderophore conjugates with photosensitizers are not taken up by mammalian cells and photodynamic effects can thus be exerted specifically on pathogenic microbes. Applications of these conjugates include highly efficient treatment of pathogenic gram-negative and -positive bacteria such as Pseudomonas aeruginosa, Escherichia coli, Streptococcus pyogenes, Staphylococcus aureus , treatment of microbial infections that often occur in chronic wounds as well as therapy of other antibiotic resistant microbial infections.

  本文介绍了铁载体-光敏剂共轭物的合成和在光动力抗微生物治疗（PACT）中的应用。该方法的优点是改善了光动力抗微生物治疗，例如对抗细菌和真菌这样的病原微生物。通过化学手段将天然存在和人工合成的铁载体结构与光活性化合物（例如氯林e6）结合，可以提高光敏剂进入细菌细胞的渗透性，并通过识别和运输铁载体的微生物蛋白质增加光敏剂的抗菌效力。通过这种方式，光敏剂可以被运输到细菌内部，否则无法穿过细胞壁和膜。在病原微生物的细胞内激活光敏剂，可以更有效地抑制细胞功能，而不是在细胞外应用。微生物的铁载体运输系统已知对细菌和真菌具有特异性。因此，铁载体共轭物与光敏剂不会被哺乳动物细胞摄取，从而可以针对病原微生物特异性地施加光动力效应。这些共轭物的应用包括高效治疗病原的革兰氏阴性和阳性细菌，例如铜绿假单胞菌，大肠杆菌，链球菌，金黄色葡萄球菌，治疗常见于慢性伤口的微生物感染以及其他抗生素耐药微生物感染的治疗。