(S)-allyl 2-(allyloxy)-4-(2-(allyloxy)-4-(4-(2-(4-aminobenzamido)-3-cyanopropanamido)benzamido)-3-methoxybenzamido)-3-methoxybenzoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-allyl 2-(allyloxy)-4-(2-(allyloxy)-4-(4-(2-(4-aminobenzamido)-3-cyanopropanamido)benzamido)-3-methoxybenzamido)-3-methoxybenzoate
• 英文别名: (5)-Allyl 2-(allyloxy)-4-(2-(allyloxy)-4-(4-(2-(4-aminobenzamido)-3-cyanopropanamido)benzamido)-3-methoxybenzamido)-3-methoxybenzoate；prop-2-enyl 4-[[4-[[4-[[(2S)-2-[(4-aminobenzoyl)amino]-3-cyanopropanoyl]amino]benzoyl]amino]-3-methoxy-2-prop-2-enoxybenzoyl]amino]-3-methoxy-2-prop-2-enoxybenzoate
• 化学式: C₄₃H₄₂N₆O₁₀
• 分子量: 802.841
• InChiKey: RHGMCPQHEUYUDM-UMSFTDKQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  59
• 可旋转键数：
  21
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  229
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (S)-allyl 2-(allyloxy)-4-(2-(allyloxy)-4-(4-(2-(4-aminobenzamido)-3-cyanopropanamido)benzamido)-3-methoxybenzamido)-3-methoxybenzoate 在 四(三苯基膦)钯 、 苯硅烷 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 (S)-allyl 4-(4-(4-(2-(4-acetamidobenzamido)-3-cyanopropanamido)benzamido)-2-(allyloxy)-3-methoxybenzamido)-2-(allyloxy)-3-methoxybenzoate
  参考文献：
  名称：

  阿比西定衍生物的合成：评估N末端酰化对抗菌活性的作用。

  摘要：

  由植物病原细菌Xanthomonas albilineans合成的肽抗生素杀菌素（albicidin）代表了一类新型的抗菌促旋酶抑制剂的最重要成员。它对革兰氏阳性和革兰氏阴性微生物显示出显着的抗菌活性。其独特的结构可能代表了开发抗菌药物的新的先导结构。在这里，我们报告了14种abicicidin衍生物的合成，这些衍生物在N端具有结构变异，主要研究了肉桂酰基，苯基丙酰基和苯甲酰基残基变异的影响。平行评估了体外的促旋酶抑制作用和最小抑菌浓度的测定。证明了在纳摩尔范围内的活性和N-酰化的重要性。

  DOI：

  10.1002/cmdc.201600231
• 作为产物：
  描述：

  2-羟基-3-甲氧基-4-硝基苯甲醛 在 2,4,6-三甲基吡啶 、 sodium chlorite 、 sodium dihydrogenphosphate 、 tin(II) chloride dihdyrate 、 三光气 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 mineral oil 、 叔丁醇 为溶剂， 反应 79.5h， 生成 (S)-allyl 2-(allyloxy)-4-(2-(allyloxy)-4-(4-(2-(4-aminobenzamido)-3-cyanopropanamido)benzamido)-3-methoxybenzamido)-3-methoxybenzoate
  参考文献：
  名称：

  阿比西丁的全合成：一种来自强酸黄单胞菌的有效抗菌陀螺酶抑制剂的前导结构。

  摘要：

  由植物病原细菌白蚁黄单胞菌（Xanthomonas albilineans）合成的肽抗生素短杆菌肽，对多种革兰氏阳性和革兰氏阴性微生物显示出显着的抗菌活性。从生产生物体或通过异源表达获得的少量白粉菌素是为生物活性图谱和结构-活性研究提供足够材料的限制因素。因此，我们开发了趋向白粉菌素的聚合全合成路线。通过三光气介导的偶联策略，实现了芳香族氨基酸之间酰胺键出乎意料的困难形成。本文提出的阿比西丁合成证实了先前确定的化学结构，并强调了该化合物的非凡抗菌活性。合成方案将提供数克量的杀菌素，以进一步分析其药物特性。

  DOI：

  10.1002/anie.201409584

文献信息

• [EN] ALBICIDIN DERIVATIVES, THEIR USE AND SYNTHESIS<br/>[FR] DÉRIVÉS D'ALBICIDINE, LEUR UTILISATION ET LEUR SYNTHÈSE
  申请人：TECH UNIVERSITÄT BERLIN

  公开号：WO2014125075A1

  公开（公告）日：2014-08-21

  The present invention relates to a antibiotically active compounds characterized by general formula (I), wherein X1, BB, BC, BD, BE and X2 are building blocks with D1, D2, D3, D4 or D5 being linkers which comprise carbon, sulphur, nitrogen, phosphor and/or oxygen atoms and which are covalently connecting the moities BA and BB, BB and BC, BC and BD, BD and BE and BE and BF, respectively, and wherein in particular the building block BC comprises an amino acid derivative. The invention relates further to said compounds for use in a method of treatment of diseases, in particular for use in a method of treatment of bacterial infections.

  本发明涉及一种抗生素活性化合物，其特征在于一般式（I），其中X1、BB、BC、BD、BE和X2是具有D1、D2、D3、D4或D5为连接物的构建块，该连接物包括碳、硫、氮、磷和/或氧原子，并以共价键连接BA和BB、BB和BC、BC和BD、BD和BE以及BE和BF的基团，特别是构建块BC包括氨基酸衍生物。该发明还涉及上述化合物用于治疗疾病的方法，特别是用于治疗细菌感染的方法。
• Total Synthesis and Biological Assessment of Novel Albicidins Discovered by Mass Spectrometric Networking
  作者：Leonard von Eckardstein、Daniel Petras、Tam Dang、Stéphane Cociancich、Souhir Sabri、Stefan Grätz、Dennis Kerwat、Maria Seidel、Alexander Pesic、Pieter C. Dorrestein、Monique Royer、John B. Weston、Roderich D. Süssmuth

  DOI：10.1002/chem.201704074

  日期：2017.11.2

  tandem mass spectrometry and spectral (molecular) networking for the discovery of novel antimicrobial compounds. We report eight new natural albicidin derivatives, four of which bear a β‐methoxy cyanoalanine or β‐methoxy asparagine as the central α‐amino acid. We present the total synthesis of these albicidins, which facilitated the unambiguous determination of the (2 S,3 R)‐stereoconfiguration which is

  天然产物代表了潜在的新型抗菌药物线索的重要来源。细胞培养中微生物的低产量通常会延迟结构阐明，甚至阻止及时发现。从Xanthomonas albilineans生产的抗革兰氏阴性抗菌化合物albicidin开始，我们描述了一种结合非靶向串联质谱和光谱（分子）网络的生物活性指导方法，用于发现新型抗菌化合物。我们报告了八种新的天然白蜡菌素衍生物，其中四个以β-甲氧基氰丙氨酸或β-甲氧基天冬酰胺为中心α-氨基酸。我们介绍了这些阿比特霉素的总合成，这有助于（2  S，3 R）-立体构型，并通过对抗菌活性的立体化学评估进行补充。
• ALBICIDIN DERIVATIVES, THEIR USE AND SYNTHESIS
  申请人：TECHNISCHE UNIVERSITÄT BERLIN

  公开号：US20150376120A1

  公开（公告）日：2015-12-31

  Antibiotically active compounds characterized by general formula (I), wherein X1, BB, BC, BD, BE and X2 are building blocks with D1, D2, D3, D4 or D5 being linkers which include carbon, sulphur, nitrogen, phosphor and/or oxygen atoms and which are covalently connecting the moities BA and BB, BB and BC, BC and BD, BD and BE and BE and BF, respectively, and wherein in particular the building block BC comprises an amino acid derivative. The compounds for use in a method of treatment of diseases, in particular for use in a method of treatment of bacterial infections are also disclosed.

  具有一般式（I）的抗生素活性化合物的特征，其中X1、BB、BC、BD、BE和X2是具有D1、D2、D3、D4或D5连接器的构建块，包括碳、硫、氮、磷和/或氧原子，并且共价连接BA和BB、BB和BC、BC和BD、BD和BE以及BE和BF的基团，其中特别是构建块BC包括一种氨基酸衍生物。该化合物用于治疗疾病的方法，特别是用于治疗细菌感染的方法。
• The Albicidin Resistance Factor AlbD Is a Serine Endopeptidase That Hydrolyzes Unusual Oligoaromatic-Type Peptides
  作者：Laura Vieweg、Julian Kretz、Alexander Pesic、Dennis Kerwat、Stefan Grätz、Monique Royer、Stéphane Cociancich、Andi Mainz、Roderich D. Süssmuth

  DOI：10.1021/jacs.5b04099

  日期：2015.6.24

  The para-aminobenzoic acid-containing peptide albicidin is a pathogenicity factor synthesized by Xanthomonas albilineans in infections of sugar cane. Albicidin is a nanomolar inhibitor of the bacterial DNA gyrase with a strong activity against various Gram-negative bacteria. The bacterium Pantoea dispersa expresses the hydrolase AlbD, conferring natural resistance against albicidin. We show that AlbD is a novel type of endopeptidase that catalyzes the cleavage of albicidin at a peptide backbone amide bond, thus abolishing its antimicrobial activity. Additionally, we determined the minimal cleavage motif of AlbD with substrates derived by Chemical synthesis. Our results clearly identify AlbD as a unique endopeptidase that is the first member of a new subfamily of peptidases. Our findings provide the molecular basis for a natural detoxification mechanism, potentially rendering a new tool in biological chemistry approaches.
• Adaptation of a Bacterial Multidrug Resistance System Revealed by the Structure and Function of AlbA
  作者：Asfandyar Sikandar、Katarina Cirnski、Giambattista Testolin、Carsten Volz、Mark Brönstrup、Olga V. Kalinina、Rolf Müller、Jesko Koehnke

  DOI：10.1021/jacs.8b08895

  日期：2018.12.5

  To combat the rise of antimicrobial resistance, the discovery of new antibiotics is paramount. Albicidin and cystobactamid are related natural product antibiotics with potent activity against Gram-positive and, crucially, Gram-negative pathogens. AlbA has been reported to neutralize albicidin by binding it with nanomolar affinity. To understand this potential resistance mechanism, we determined structures of AlbA and its complex with albicidin. The structures revealed AlbA to be comprised of two domains, each unexpectedly resembling the multiantibiotic neutralizing protein TipA. Binding of the long albicidin molecule was shared pseudosymmetrically between the two domains. The structure also revealed an unexpected chemical modification of albicidin, which we demonstrate to be promoted by AlbA, and to reduce albicidin potency; we propose a mechanism for this reaction. Overall, our findings suggest that AlbA arose through internal duplication in an ancient TipA-like gene, leading to a new binding scaffold adapted to the sequestration of long-chain antibiotics.