1-O-benzyl-4,6-O-diacetyl-3-O-((R)-phenylsulfonylethyl-propion-2-yl)-N-acetyl-α-D-glucosamine | 202464-71-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-O-benzyl-4,6-O-diacetyl-3-O-((R)-phenylsulfonylethyl-propion-2-yl)-N-acetyl-α-D-glucosamine
• 英文别名: 2-(benzenesulfonyl)ethyl (2R)-2-[(2R,3S,4R,5R,6S)-5-acetamido-3-acetyloxy-2-(acetyloxymethyl)-6-phenylmethoxyoxan-4-yl]oxypropanoate
• CAS: 202464-71-9
• 化学式: C₃₀H₃₇NO₁₂S
• 分子量: 635.689
• InChiKey: RBFRYMXHYSKGMV-JEHFRJJUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  44
• 可旋转键数：
  17
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  178
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  1-O-benzyl-4,6-O-diacetyl-3-O-((R)-phenylsulfonylethyl-propion-2-yl)-N-acetyl-α-D-glucosamine 在 palladium 10% on activated carbon 、 水 、 氢气 、 金刚烷酰氯 作用下， 以 吡啶 、 甲醇 、 乙腈 为溶剂， -10.0~20.0 ℃ 、101.33 kPa 条件下， 反应 10.5h， 生成 methyl (2R)-3-(((((2R,3R,4R,5S,6R)-3-acetamido-5-acetoxy-6-(acetoxymethyl)-4-(((R)-1-oxo-1-(2-(phenylsulfonyl)ethoxy)propan-2-yl)oxy)tetrahydro-2H-pyran-2-yl)oxy)(hydroxy)phosphoryl)oxy)-2-(((E)-3,7-dimethylocta-2,6-dien-1-yl)oxy)propanoate
  参考文献：
  名称：

  Synthesis of Modified Peptidoglycan Precursor Analogues for the Inhibition of Glycosyltransferase

  摘要：

  The peptidoglycan glycosyltransferases (GTs) are essential enzymes that catalyze the polymerization of On OH glycan chains of the bacterial cell wall from lipid II and thus constitute a validated antibacterial target. Their enzymatic cavity is composed of a donor site for the growing glycan chain (where the inhibitor moenomycin binds) and an acceptor site for lipid II substrate. In order to find lead inhibitors able to fill this large active site, we have synthesized a series of substrate analogues of lipid I and lipid II with variations in the lipid, the pyrophosphate, and the peptide moieties and evaluated their biological effect on the GT activity of E. coli PBP1b and their antibacterial potential. We found several compounds able to inhibit the GT activity in vitro and cause growth defect in Bacillus subtilis. The more active was C16-phosphoglycerate-MurNAc-(L-Alao-D-Glu)-GIcNAc, which also showed antibacterial activity. These molecules are promising leads for the design of new antibacterial GT inhibitors.

  DOI：

  10.1021/ja302099u
• 作为产物：
  描述：

  2-(苯基磺酰基)乙醇 在 吡啶 、 4-二甲氨基吡啶 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 1-O-benzyl-4,6-O-diacetyl-3-O-((R)-phenylsulfonylethyl-propion-2-yl)-N-acetyl-α-D-glucosamine
  参考文献：
  名称：

  脂质 I 的全合成

  摘要：

  据报道，脂质 I (4) 是细菌细胞壁（肽聚糖）生物合成途径中的膜相关中间体的全合成。这种高度趋同的合成将使对细菌耐药机制的进一步研究成为可能，并可能为开发具有新作用模式的新型化疗药物提供见解。

  DOI：

  10.1021/ja016082o

文献信息

• Total Synthesis of Dansylated Park's Nucleotide for High-Throughput MraY Assays
  作者：Stephanie Wohnig、Anatol P. Spork、Stefan Koppermann、Gottfried Mieskes、Nicolas Gisch、Reinhard Jahn、Christian Ducho

  DOI：10.1002/chem.201604279

  日期：2016.12.5

  membrane protein translocase I (MraY) is a key enzyme in bacterial peptidoglycan biosynthesis. It is therefore frequently discussed as a target for the development of novel antibiotics. The screening of compound libraries for the identification of MraY inhibitors is enabled by an established fluorescence‐based MraY assay. However, this assay requires a dansylated derivative of the bacterial biosynthetic

  膜蛋白转位酶I（MraY）是细菌肽聚糖生物合成中的关键酶。因此，经常将其作为开发新型抗生素的靶标进行讨论。通过已建立的基于荧光的MraY分析，可以筛选用于鉴定MraY抑制剂的化合物库。然而，该测定需要细菌生物合成中间体Park的核苷酸的丹磺酰化衍生物作为MraY底物。从细菌中分离出Park的核苷酸并随后进行丹磺酰化只能提供有限量的这种底物，从而妨碍了高通量筛选MraY抑制剂。因此，在提供这种有希望的药物靶标时，有效提供丹磺酰化的Park核苷酸是一个主要的瓶颈。在这项工作中，
• The First Total Synthesis of Bacterial Cell Wall Precursor UDP−<i>N</i>-Acetylmuramyl-Pentapeptide (Park Nucleotide)
  作者：Stephen A. Hitchcock、Clark N. Eid、James A. Aikins、Mohammad Zia-Ebrahimi、Larry C. Blaszczak

  DOI：10.1021/ja973172d

  日期：1998.3.1
• Synthesis of Modified Peptidoglycan Precursor Analogues for the Inhibition of Glycosyltransferase
  作者：Shrinivas Dumbre、Adeline Derouaux、Eveline Lescrinier、André Piette、Bernard Joris、Mohammed Terrak、Piet Herdewijn

  DOI：10.1021/ja302099u

  日期：2012.6.6

  The peptidoglycan glycosyltransferases (GTs) are essential enzymes that catalyze the polymerization of On OH glycan chains of the bacterial cell wall from lipid II and thus constitute a validated antibacterial target. Their enzymatic cavity is composed of a donor site for the growing glycan chain (where the inhibitor moenomycin binds) and an acceptor site for lipid II substrate. In order to find lead inhibitors able to fill this large active site, we have synthesized a series of substrate analogues of lipid I and lipid II with variations in the lipid, the pyrophosphate, and the peptide moieties and evaluated their biological effect on the GT activity of E. coli PBP1b and their antibacterial potential. We found several compounds able to inhibit the GT activity in vitro and cause growth defect in Bacillus subtilis. The more active was C16-phosphoglycerate-MurNAc-(L-Alao-D-Glu)-GIcNAc, which also showed antibacterial activity. These molecules are promising leads for the design of new antibacterial GT inhibitors.
• The Total Synthesis of Lipid I
  作者：Michael S. VanNieuwenhze、Scott C. Mauldin、Mohammad Zia-Ebrahimi、James A. Aikins、Larry C. Blaszczak

  DOI：10.1021/ja016082o

  日期：2001.7.1

  A total synthesis of lipid I (4), a membrane-associated intermediate in the bacterial cell wall (peptidoglycan) biosynthesis pathway, is reported. This highly convergent synthesis will enable further studies on bacterial resistance mechanisms and may provide insight toward the development of new chemotherapeutic agents with novel modes of action.

  据报道，脂质 I (4) 是细菌细胞壁（肽聚糖）生物合成途径中的膜相关中间体的全合成。这种高度趋同的合成将使对细菌耐药机制的进一步研究成为可能，并可能为开发具有新作用模式的新型化疗药物提供见解。