3,7,11,15,19,23,27-heptamethyloctaeicosa-2Z,6Z,10Z,14Z,18E,22E,26-heptaene-1-ol phosphate diammonium salt

• 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: 3,7,11,15,19,23,27-heptamethyloctaeicosa-2Z,6Z,10Z,14Z,18E,22E,26-heptaene-1-ol phosphate diammonium salt
• 英文别名: heptaprenyl monophosphate diammonium salt；azane;[(2Z,6Z,10Z,14Z,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaenyl] dihydrogen phosphate
• 化学式: C₃₅H₅₉O₄P*2H₃N
• 分子量: 608.886
• InChiKey: DAJWAKPLFULGPE-KVERTUSFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.58
• 重原子数：
  41
• 可旋转键数：
  21
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  67.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,7,11,15,19,23,27-heptamethyloctaeicosa-2Z,6Z,10Z,14Z,18E,22E,26-heptaene-1-ol phosphate diammonium salt 在 lithium hydroxide monohydrate 、 1-甲基氯化咪唑鎓 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 N-acetyl-1-[P'-[(2Z,6Z,10Z,14Z,18E,22E)-3,7,11,15,19,23,27-heptamethyl-2,6,10,14,18,22,26-octacosaheptaen-1-yl]diammonium diphosphate]muramic acid
  参考文献：
  名称：

  N-Methylimidazolium chloride-catalyzed pyrophosphate formation: Application to the synthesis of Lipid I and NDP-sugar donors

  摘要：

  N-Methylimidazolium chloride is found to catalyze a coupling reaction between monophosphates and activated phosphorous-nitrogen intermediates such as a phosphorimidazolide and phosphoromorpholidate to form biologically important unsymmetrical pyrophosphate diesters. The catalyst is much more active, cheaper, and less explosive than 1H-tetrazole, known as the best catalyst for the pyrophosphate formation over a decade. The mild and neutral reaction conditions are compatible with allylic pyrophosphate formation in Lipid I syntheisis. (31)P NMR experiments suggest that the catalyst acts not only as an acid but also as a nucleophile to form cationic and electrophilic phosphor-N-methylimidazolide intermediates in the pyrophosphate formation. (c) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.061
• 作为产物：
  描述：

  橙花醇 在 吡啶 、 四氮唑 、 六甲基磷酰三胺 、 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 异丙醚 、 三苯基甲烷 、 水 、 sodium methylate 、 lithium 、 sodium hydride 、 potassium carbonate 、 对甲苯磺酸 、 乙胺 、 高碘酸 、 sodium iodide 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 乙醚 、 乙醇 、 正己烷 、 水 、 丙酮 、 甲苯 、 mineral oil 为溶剂， 反应 194.39h， 生成 3,7,11,15,19,23,27-heptamethyloctaeicosa-2Z,6Z,10Z,14Z,18E,22E,26-heptaene-1-ol phosphate diammonium salt
  参考文献：
  名称：

  金黄色葡萄球菌青霉素结合蛋白 2 可以使用源自万古霉素耐药菌株的 Depsi-Lipid II 来合成细胞壁

  摘要：

  耐万古霉素金黄色葡萄球菌（S. aureus）（VRSA）使用含有缩酚肽的修饰细胞壁前体来生物合成肽聚糖。转糖基酶负责肽聚糖的聚合，青霉素结合蛋白 2 (PBP2) 在野生型金黄色葡萄球菌的几种转糖基酶的聚合中起主要作用。然而，尚不清楚 VRSA 是否使用 PBP2 处理含有缩酚肽的肽聚糖前体。在这里，我们描述了 depsi-lipid I（VRSA 的细胞壁前体）的全合成。通过使用这种化学方法，我们制备了 depsi-lipid II 类似物作为无细胞转糖基化系统的底物。重建的系统表明，金黄色葡萄球菌的 PBP2能够像其正常底物一样有效地处理 depsi-lipid II 中间体。此外，该系统还成功地用于证明两种抗生素莫诺霉素和万古霉素作用方式的差异。

  DOI：

  10.1002/chem.201301074

文献信息

• Synthesis of a Comprehensive Polyprenol Library for the Evaluation of Bacterial Enzyme Lipid Substrate Specificity
  作者：Baolin Wu、Robert Woodward、Liuqing Wen、Xuan Wang、Guohui Zhao、Peng George Wang

  DOI：10.1002/ejoc.201301089

  日期：2013.12

  Polyprenols, a type of universal glycan lipid carrier, play important roles for glycan bio-assembly in wide variety of living systems. Chemical synthesis of natural polyisoprenols such as undecaprenol and dolichols, but especially their homologs, could serves as a powerful molecular tool to dissect and define the functions of enzymes involved in glycan biosynthesis. In this paper, we report an efficient

  多元醇是一种通用的聚糖脂质载体，在多种生物系统中对聚糖的生物组装起着重要的作用。天然的聚异戊二烯，例如十一碳烯醇和二元醇的化学合成，尤其是它们的同系物，可以作为一种强大的分子工具来分析和确定参与聚糖生物合成的酶的功能。在本文中，我们报告了一种有效且可靠的方法，该方法通过使用关键的双功能（Z，Z）-二异戊二烯结构单元的碱基介导的迭代偶联方法来构建此类疏水分子。还证明了与N-乙酰基-D-葡糖胺（GalNAc）与一组合成的脂质类似物形成聚戊二烯焦磷酸连接的GalNAc（GalNAc-PP-脂质）缀合物的连接。
• Synthesis of Heptaprenyl−Lipid IV to Analyze Peptidoglycan Glycosyltransferases
  作者：Yi Zhang、Eric J. Fechter、Tsung-Shing Andrew Wang、Dianah Barrett、Suzanne Walker、Daniel E. Kahne

  DOI：10.1021/ja069060g

  日期：2007.3.1

  tremendous potential as antibiotic targets, but the potential has not yet been realized. Mechanistic studies have been hampered by a lack of substrates to monitor enzymatic activity. We report here the total synthesis of heptaprenyl−Lipid IV and its use to study two different PGTs from E. coli. We show that one PGT can couple Lipid IV to itself whereas the other can only couple Lipid IV to Lipid II. These

  细菌被包含肽聚糖层的细胞壁包围，肽聚糖的完整性对于细菌的生存至关重要。在肽聚糖生物合成的最后阶段，肽聚糖糖基转移酶 (PGTs；也称为转糖基酶) 催化脂质 II 聚合形成线性聚糖链。PGTs 作为抗生素靶点具有巨大的潜力，但其潜力尚未实现。由于缺乏监测酶活性的底物，机制研究受到阻碍。我们在此报告了庚烯基-脂质 IV 的全合成及其用于研究来自大肠杆菌的两种不同 PGT。我们表明一个 PGT 可以将脂质 IV 与其自身结合，而另一个只能将脂质 IV 与脂质 II 结合。
• Transpeptidase-Mediated Incorporation of <scp>d</scp>-Amino Acids into Bacterial Peptidoglycan
  作者：Tania J. Lupoli、Hirokazu Tsukamoto、Emma H. Doud、Tsung-Shing Andrew Wang、Suzanne Walker、Daniel Kahne

  DOI：10.1021/ja2040656

  日期：2011.7.20

  The beta-lactams are the most important class of antibiotics in clinical use. Their lethal targets are the transpeptidase domains of penicillin binding proteins (PBPs), which catalyze the cross-linking of bacterial peptidoglycan (PG) during cell wall synthesis. The transpeptidation reaction occurs in two steps, the first being formation of a covalent enzyme intermediate and the second involving attack of an amine on this intermediate. Here we use defined PG substrates to dissect the individual steps catalyzed by a purified E. coli transpeptidase. We demonstrate that this transpeptidase accepts a set of structurally diverse D-amino acid substrates and incorporates them into PG fragments. These results provide new information on donor and acceptor requirements as well as a mechanistic basis for previous observations that noncanonical D-amino acids can be introduced into the bacterial cell wall.
• <i>Staphylococcus aureus</i>Penicillin-Binding Protein 2 Can Use Depsi-Lipid II Derived from Vancomycin-Resistant Strains for Cell Wall Synthesis
  作者：Jun Nakamura、Hidenori Yamashiro、Hiroto Miya、Kenzo Nishiguchi、Hideki Maki、Hirokazu Arimoto

  DOI：10.1002/chem.201301074

  日期：2013.9.2

  depsipeptide‐containing peptidoglycan precursor by using PBP2. Here, we describe the total synthesis of depsi‐lipid I, a cell‐wall precursor of VRSA. By using this chemistry, we prepared a depsi‐lipid II analogue as substrate for a cell‐free transglycosylation system. The reconstituted system revealed that the PBP2 of S. aureus is able to process a depsi‐lipid II intermediate as efficiently as its normal substrate

  耐万古霉素金黄色葡萄球菌（S. aureus）（VRSA）使用含有缩酚肽的修饰细胞壁前体来生物合成肽聚糖。转糖基酶负责肽聚糖的聚合，青霉素结合蛋白 2 (PBP2) 在野生型金黄色葡萄球菌的几种转糖基酶的聚合中起主要作用。然而，尚不清楚 VRSA 是否使用 PBP2 处理含有缩酚肽的肽聚糖前体。在这里，我们描述了 depsi-lipid I（VRSA 的细胞壁前体）的全合成。通过使用这种化学方法，我们制备了 depsi-lipid II 类似物作为无细胞转糖基化系统的底物。重建的系统表明，金黄色葡萄球菌的 PBP2能够像其正常底物一样有效地处理 depsi-lipid II 中间体。此外，该系统还成功地用于证明两种抗生素莫诺霉素和万古霉素作用方式的差异。
• N-Methylimidazolium chloride-catalyzed pyrophosphate formation: Application to the synthesis of Lipid I and NDP-sugar donors
  作者：Hirokazu Tsukamoto、Daniel Kahne

  DOI：10.1016/j.bmcl.2011.04.061

  日期：2011.9

  N-Methylimidazolium chloride is found to catalyze a coupling reaction between monophosphates and activated phosphorous-nitrogen intermediates such as a phosphorimidazolide and phosphoromorpholidate to form biologically important unsymmetrical pyrophosphate diesters. The catalyst is much more active, cheaper, and less explosive than 1H-tetrazole, known as the best catalyst for the pyrophosphate formation over a decade. The mild and neutral reaction conditions are compatible with allylic pyrophosphate formation in Lipid I syntheisis. (31)P NMR experiments suggest that the catalyst acts not only as an acid but also as a nucleophile to form cationic and electrophilic phosphor-N-methylimidazolide intermediates in the pyrophosphate formation. (c) 2011 Elsevier Ltd. All rights reserved.