(2Z,6E,13E)-1-bromo-3,8,8,14,18-pentamethyl-11-methylidenenonadeca-2,6,13,17-tetraene | 916045-41-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (2Z,6E,13E)-1-bromo-3,8,8,14,18-pentamethyl-11-methylidenenonadeca-2,6,13,17-tetraene
• CAS: 916045-41-5
• 化学式: C₂₅H₄₁Br
• 分子量: 421.505
• InChiKey: JQVDYYNMYXUNLR-RSYGDTPCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.2
• 重原子数：
  26
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  (2Z,6E,13E)-1-bromo-3,8,8,14,18-pentamethyl-11-methylidenenonadeca-2,6,13,17-tetraene 在 sodium chlorite 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 四丁基氟化铵 、 sodium hydride 、 碳酸氢钠 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 17.0h， 生成 methyl (R)-3-(3,4-dimethoxybenzyloxy)-2-[(2Z,6E,13E)-3,8,8,14,18-pentamethyl-11-methylenenonadeca-2,6,13,17-tertaen-1-yloxy]propanoate
  参考文献：
  名称：

  Degradation and Reconstruction of Moenomycin A and Derivatives:  Dissecting the Function of the Isoprenoid Chain

  摘要：

  Moenomycin A is the only known natural product that inhibits peptidoglycan biosynthesis by binding the bacterial transglycosylases. We describe a degradation/reconstruction route to manipulate the reducing end of moenomycin A. A comparison of the biological and enzyme inhibitory activity of moenomycin A and an analogue containing a nerol lipid in place of the natural C25 lipid chain provides insight into the role of the moenocinol unit. Our results show that a lipid chain having ten carbons in moenocinol is sufficient for enzyme inhibition, but a longer chain is required for biological acitivity, apparently because the molecule must partition into biological membranes to reach its target in bacterial cells.

  DOI：

  10.1021/ja065905c
• 作为产物：
  描述：

  (2Z,6E,13E)-3,8,8,14,18-五甲基-11-亚甲基-2,6,13,17-十九四烯-1-醇 在 三溴化磷 作用下， 以 乙醚 为溶剂， 反应 1.0h， 以80%的产率得到(2Z,6E,13E)-1-bromo-3,8,8,14,18-pentamethyl-11-methylidenenonadeca-2,6,13,17-tetraene
  参考文献：
  名称：

  [EN] MOENOMYCIN ANALOGS, METHODS OF SYNTHESIS, AND USES THEREOF
  [FR] ANALOGUES DE LA MOÉNOMYCINE, PROCÉDÉS DE SYNTHÈSE ET UTILISATIONS DE CEUX-CI

  摘要：

  公开号：

  WO2009046314A3

文献信息

• Functional and Structural Analysis of a Key Region of the Cell Wall Inhibitor Moenomycin
  作者：Shinichiro Fuse、Hirokazu Tsukamoto、Yanqiu Yuan、Tsung-Shing Andrew Wang、Yi Zhang、Megan Bolla、Suzanne Walker、Piotr Sliz、Daniel Kahne

  DOI：10.1021/cb100048q

  日期：2010.7.16

  pentasaccharide to the moenocinyl chain. This moiety contains two negatively charged groups, a phosphoryl group and a carboxylate. Both the phosphoryl group and the carboxylate have previously been implicated in target binding but the role of the carboxylate has not been explored in detail. Here we report the synthesis of six MmA analogues designed to probe the importance of the phosphoglycerate. These

  Moenomycin A (MmA) 属于天然产物家族，通过与肽聚糖糖基转移酶（制造肽聚糖聚糖链的酶）结合来抑制肽聚糖生物合成。MmA 非常有效，但其临床效用受到较差的物理化学性质的阻碍。Moenomycin 包含三个结构不同的区域：一个五糖、一个磷酸甘油酸酯和一个 C25 异戊二烯基（moenocinyl）脂质尾，该分子的名称由此而来。磷酸甘油酸酯部分将五糖连接到 moenocinyl 链。该部分包含两个带负电荷的基团，一个磷酰基和一个羧酸根。磷酰基和羧酸根之前都与靶标结合有关，但尚未详细探讨羧酸根的作用。在这里，我们报告了六种 MmA 类似物的合成，旨在探讨磷酸甘油酸的重要性。评估了这些类似物的抗菌和酶抑制活性；磷酸甘油酸和蛋白质靶标之间的特定接触通过 X 射线晶体学结合分子建模进行评估。磷酸甘油酸酯链的磷酰基和羧酸盐都在靶标结合中起作用。羧酸盐的负电荷，而不是其特定结构，似乎是结合的
• MOENOMYCIN ANALOGS, METHODS OF SYNTHESIS, AND USES THEREOF
  申请人：Kahne Daniel

  公开号：US20110136759A1

  公开（公告）日：2011-06-09

  The present invention provides novel moenomycin analogs as well as pharmaceutical compositions thereof, methods of synthesis, and methods of use in treating an infection by administering an inventive compound to a subject in need thereof. The moenomycin analogs may be prepared synthetically, biosynthetically, or semi-synthetically. The analogs are particularly useful in treating or preventing infections caused by Gram-positive organisms. Certain inventive compounds may have a broader spectrum of coverage, which includes Gram-negative organisms.

  本发明提供了新型的莫诺霉素类似物及其制药组合物，合成方法以及将创新化合物用于治疗感染的方法，通过将创新化合物给予需要治疗的受试者来治疗感染。莫诺霉素类似物可以通过化学合成，生物合成或半合成的方式制备。这些类似物在治疗或预防由革兰氏阳性菌引起的感染中特别有用。某些创新化合物可能具有更广泛的覆盖范围，包括革兰氏阴性菌。
• [EN] MOENOMYCIN ANALOGS, METHODS OF SYNTHESIS, AND USES THEREOF<br/>[FR] ANALOGUES DE LA MOÉNOMYCINE, PROCÉDÉS DE SYNTHÈSE ET UTILISATIONS DE CEUX-CI
  申请人：HARVARD COLLEGE

  公开号：WO2009046314A3

  公开（公告）日：2009-05-22
• Degradation and Reconstruction of Moenomycin A and Derivatives:  Dissecting the Function of the Isoprenoid Chain
  作者：Masaatsu Adachi、Yi Zhang、Catherine Leimkuhler、Binyuan Sun、John V. LaTour、Daniel E. Kahne

  DOI：10.1021/ja065905c

  日期：2006.11.1

  Moenomycin A is the only known natural product that inhibits peptidoglycan biosynthesis by binding the bacterial transglycosylases. We describe a degradation/reconstruction route to manipulate the reducing end of moenomycin A. A comparison of the biological and enzyme inhibitory activity of moenomycin A and an analogue containing a nerol lipid in place of the natural C25 lipid chain provides insight into the role of the moenocinol unit. Our results show that a lipid chain having ten carbons in moenocinol is sufficient for enzyme inhibition, but a longer chain is required for biological acitivity, apparently because the molecule must partition into biological membranes to reach its target in bacterial cells.