2-脱氧-3-O-[(3R)-3-羟基十四烷酰基]-2-{[(3R)-3-羟基十四烷酰基]氨基}-1-O-膦酰-alpha-D-吡喃葡萄糖 | 86559-73-1

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 糖脂
• 中文名称: 2-脱氧-3-O-[(3R)-3-羟基十四烷酰基]-2-{[(3R)-3-羟基十四烷酰基]氨基}-1-O-膦酰-alpha-D-吡喃葡萄糖
• 中文别名: DNA-PK抑制剂(COMPOUND401)
• 英文名称: 2-deoxy-3-O<(R)-3-hydroxytetradecanoyl>-2-<<(R)-3-hydroxytetradecanoyl>amino>-α-D-glucopyranosyl-1-phosphate
• 英文别名: 2-<(R)-3-hydroxytetradecanamido>-3-O-<(R)-3-hydroxytetradecanoyl>-2-deoxy-α-D-glucopyranosyl-1-phosphate；2-deoxy-2-<(R)-3-hydroxytetradecanamido>-3-O-<(R)-3-hydroxytetradecanoyl>-α-D-glucopyranose 1-phosphate；2,3-bis-(3R-hydroxytetradecanoyl)-α-D-glucosamine 1-phosphate；Lipid X；[(2R,3S,4R,5R,6R)-3-hydroxy-2-(hydroxymethyl)-5-[[(3R)-3-hydroxytetradecanoyl]amino]-6-phosphonooxyoxan-4-yl] (3R)-3-hydroxytetradecanoate
• CAS: 86559-73-1
• 化学式: C₃₄H₆₆NO₁₂P
• 分子量: 711.871
• InChiKey: HEHQDWUWJVPREQ-XQJZMFRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  48
• 可旋转键数：
  30
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  212
• 氢给体数：
  7
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  2-脱氧-3-O-[(3R)-3-羟基十四烷酰基]-2-{[(3R)-3-羟基十四烷酰基]氨基}-1-O-膦酰-alpha-D-吡喃葡萄糖 以 甲醇 、 水 为溶剂， 生成
  参考文献：
  名称：

  方便合成2-脱氧-2-[（（R）-1-羟基十四烷酰胺基] -3-O-[（R）-3-羟基十四烷酰基]-α-d-吡喃葡萄糖1-磷酸（脂质X）

  摘要：

  摘要2-脱氧-2-[（（R）-3-羟基十四烷酰胺基] -3-O-[（R）-3-羟基十四烷酰基]-α-d-吡喃葡萄糖的结晶三（羟甲基）氨基甲烷（“ Tris”）盐由2-氨基-2-脱氧-d-葡萄糖盐酸盐经五个步骤合成了1-磷酸酯（脂质X），总产率约为50％。关键步骤是丁基锂催化的4，6-O-亚苄基-2-[（R）-3-苄氧基四癸酰胺基] -2-脱氧-d-吡喃葡萄糖的1-O-（二苄基）磷酸化。然后将产物3-（R）-3-苄氧基十四烷酰化，并通过催化氢化除去苄基和亚苄基。

  DOI：

  10.1016/0008-6215(87)80202-1
• 作为产物：
  描述：

  4,6-O-benzylidene-2-<(R)-3-benzyloxytetradecanamido>-3-O-<(R)-3-benzyloxytetradecanoyl>-2-deoxy-α-D-glucopyranose 1-(dibenzyl phosphate) 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 水 为溶剂， 40.0 ℃ 、999.99 kPa 条件下， 反应 2.0h， 以96%的产率得到2-脱氧-3-O-[(3R)-3-羟基十四烷酰基]-2-{[(3R)-3-羟基十四烷酰基]氨基}-1-O-膦酰-alpha-D-吡喃葡萄糖
  参考文献：
  名称：

  方便合成2-脱氧-2-[（（R）-1-羟基十四烷酰胺基] -3-O-[（R）-3-羟基十四烷酰基]-α-d-吡喃葡萄糖1-磷酸（脂质X）

  摘要：

  摘要2-脱氧-2-[（（R）-3-羟基十四烷酰胺基] -3-O-[（R）-3-羟基十四烷酰基]-α-d-吡喃葡萄糖的结晶三（羟甲基）氨基甲烷（“ Tris”）盐由2-氨基-2-脱氧-d-葡萄糖盐酸盐经五个步骤合成了1-磷酸酯（脂质X），总产率约为50％。关键步骤是丁基锂催化的4，6-O-亚苄基-2-[（R）-3-苄氧基四癸酰胺基] -2-脱氧-d-吡喃葡萄糖的1-O-（二苄基）磷酸化。然后将产物3-（R）-3-苄氧基十四烷酰化，并通过催化氢化除去苄基和亚苄基。

  DOI：

  10.1016/0008-6215(87)80202-1

文献信息

• Chemical syntheses of lipid X and lipid Y, acyl glucosamine 1-phosphates isolated from escherichia coli mutants
  作者：Shoichi Kusumoto、Michiharu Yamamoto、Tetsuo Shiba

  DOI：10.1016/0040-4039(84)80116-1

  日期：1984.1

  (R)-3-hydroxytetradecanoyl-glucosamine 1-phosphate and 2-N-(R) -3-hexadecanoyloxytetradecanoyl-3-O-(R)-3-hydroxytetradecanoylglucosamine 1-phosphate, were synthesized and identified with natural lipid X and lipid Y respectively.

  两种新的磷脂2-N; 合成了3-O-双（R）-3-羟基十四烷酰基葡萄糖胺1-磷酸酯和2-N-（R）-3-十六烷酰氧基十四烷酰基-3-O-（R）-3-羟基十四烷酰基葡糖胺1-磷酸天然脂质X和脂质Y分别。
• Lipid A and related compounds. XI New, efficient synthesis of lipid X.
  作者：KIYOSHI IKEDA、TOSHIO TAKAHASHI、CHIKAKO SHIMIZU、SHINICHI NAKAMOTO、KAZUO ACHIWA

  DOI：10.1248/cpb.35.1383

  日期：——

  A new methodology for chemical differentiation of one amino and four hydroxyl groups of glucosamine derivatives and its application for the synthesis of lipid X are described.

  描述了一种化学区分葡萄糖胺衍生物的一个氨基和四个羟基的新方法及其在脂质X合成中的应用。
• A NEW METHODOLOGY FOR CHEMOSELECTION OF ONE AMINO AND FOUR HYDROXYL GROUPS OF GLUCOSAMINE DERIVATIVES AND ITS USE FOR SYNTHESIS OF LIPID X
  作者：Toshio Takahashi、Chikako Shimizu、Shinichi Nakamoto、Kiyoshi Ikeda、Kazuo Achiwa

  DOI：10.1248/cpb.33.1760

  日期：——

  New development of a general key-intermediate for synthesis of lipid A and related compounds and its conversion into lipid X are described.

  介绍了合成脂质 A 和相关化合物的通用关键中间体的新进展，以及将其转化为脂质 X 的情况。
• The substrate-binding cap of the UDP-diacylglucosamine pyrophosphatase LpxH is highly flexible, enabling facile substrate binding and product release
  作者：Heather O. Bohl、Pek Ieong、John K. Lee、Thomas Lee、Jayakanth Kankanala、Ke Shi、Özlem Demir、Kayo Kurahashi、Rommie E. Amaro、Zhengqiang Wang、Hideki Aihara

  DOI：10.1074/jbc.ra118.002503

  日期：2018.5

  outer leaflet is composed of the glycolipid lipopolysaccharide (LPS), which guards against hydrophobic toxins, including many antibiotics. Therefore, LPS synthesis in bacteria is an attractive target for antibiotic development. LpxH is a pyrophosphatase involved in LPS synthesis, and previous structures revealed that LpxH has a helical cap that binds its lipid substrates. Here, crystallography and hydrogen-deuterium

  革兰氏阴性细菌被次生膜包围，其外层由糖脂脂多糖 (LPS) 组成，可防止疏水性毒素，包括许多抗生素。因此，细菌中脂多糖的合成是抗生素开发的一个有吸引力的目标。LpxH 是一种参与 LPS 合成的焦磷酸酶，之前的结构表明 LpxH 具有与其脂质底物结合的螺旋帽。在这里，晶体学和氢-氘交换 MS 为 LpxH 中高度灵活的底物结合帽提供了证据。此外，分子动力学模拟揭示了帽的螺旋如何打开以允许基质进入。LpxH 变体的活性测定支持了预测的开放机制。最后，我们从生化角度证实了 LpxH 受到先前鉴定的抗菌化合物的抑制，确定了该抑制剂的效力，并模拟了其在 LpxH 活性位点的结合模式。总之，我们的工作提供了证据，证明 LpxH 的底物结合帽是高度动态的，从而允许在加帽螺旋之间轻松进行底物结合和产物释放。我们的结果也为合理设计更有效的 LpxH 抑制剂铺平了道路。
• An Alternative Route for UDP-Diacylglucosamine Hydrolysis in Bacterial Lipid A Biosynthesis
  作者：Louis E. Metzger、Christian R. H. Raetz

  DOI：10.1021/bi1008744

  日期：2010.8.10

  The outer leaflet of the outer membranes of Gram-negative bacteria is composed primarily of lipid A, the hydrophobic anchor of lipopolysaccharide. Like Escherichia coli, most Gram-negative bacteria encode one copy of each of the nine genes required for lipid A biosynthesis. An important exception exists in the case of the fourth enzyme, LpxH, a peripheral membrane protein that hydrolyzes UDP-2,3-diacylglucosamine to form 2,3-diacylglucosamine 1-phosphate and UMP by catalyzing the attack of water at the alpha-P atom. Many Gram-negative organisms, including all alpha-proteobacteria and diverse environmental isolates, lack LpxH. Here, we report a distinct UDP-2,3-diacylglucosamine pyrophosphatase, designated LpxI, which has no sequence similarity to LpxH but generates the same products by a different route. LpxI was identified because its structural gene is located between lpxA and lpxB in Caulobacter crescentus. The lpxI gene rescues the conditional lethality of lpxH-deficient E. coli. Lysates of E. coli in which C. crescentus LpxI (CcLpxI) is overexpressed display high levels of UDP-2,3-diacylglucosamine pyrophosphatase activity. CcLpxI was purified to >90% homogeneity. CcLpxI is stimulated by divalent cations and is inhibited by EDTA. Unlike E. coli LpxH, CcLpxI is not inhibited by an increase in the concentration of detergent, and its pH dependency is different. When the CcLpxI reaction is conducted in the presence of (H2O)-O-18, the O-18 is incorporated exclusively into the 2,3-diacylglucosamine I-phosphate product, as judged by mass spectrometry, demonstrating that CcLpxI catalyzes the attack of water on the beta-P atom of UDP-2,3-diacylglucosamine.