tert-butyl (2S)-2-[[(1S)-2-[[1-[3-[[(1S,2S)-1-[[(3aR,4S,6R,6aR)-2,2-diethyl-6-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]oxy]-1-[(3aR,4R,6R,6aR)-4-(2,4-dioxopyrimidin-1-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]-3-[(2-methylpropan-2-yl)oxy]-3-oxopropan-2-yl]amino]propylamino]-1-oxoheptadecan-2-yl]-[(2,4-dimethoxyphenyl)methyl]amino]-2-oxo-1-[(6S)-2-(2,2,2-trichloroethoxysulfonylamino)-1,4,5,6-tetrahydropyrimidin-6-yl]ethyl]carbamoylamino]-3-methylbutanoate | 1234357-55-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl (2S)-2-[[(1S)-2-[[1-[3-[[(1S,2S)-1-[[(3aR,4S,6R,6aR)-2,2-diethyl-6-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]oxy]-1-[(3aR,4R,6R,6aR)-4-(2,4-dioxopyrimidin-1-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]-3-[(2-methylpropan-2-yl)oxy]-3-oxopropan-2-yl]amino]propylamino]-1-oxoheptadecan-2-yl]-[(2,4-dimethoxyphenyl)methyl]amino]-2-oxo-1-[(6S)-2-(2,2,2-trichloroethoxysulfonylamino)-1,4,5,6-tetrahydropyrimidin-6-yl]ethyl]carbamoylamino]-3-methylbutanoate
• CAS: 1234357-55-1
• 化学式: C₈₀H₁₃₀Cl₃N₁₁O₂₃S
• 分子量: 1752.4
• InChiKey: HTPGBOPEQLJYPB-FIDUXWSCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.4
• 重原子数：
  118
• 可旋转键数：
  51
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  414
• 氢给体数：
  8
• 氢受体数：
  25

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S)-2-[[(1S)-2-[[1-[3-[[(1S,2S)-1-[[(3aR,4S,6R,6aR)-2,2-diethyl-6-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]oxy]-1-[(3aR,4R,6R,6aR)-4-(2,4-dioxopyrimidin-1-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]-3-[(2-methylpropan-2-yl)oxy]-3-oxopropan-2-yl]amino]propylamino]-1-oxoheptadecan-2-yl]-[(2,4-dimethoxyphenyl)methyl]amino]-2-oxo-1-[(6S)-2-(2,2,2-trichloroethoxysulfonylamino)-1,4,5,6-tetrahydropyrimidin-6-yl]ethyl]carbamoylamino]-3-methylbutanoate 在 锌 、 三氟乙酸 作用下， 以 四氢呋喃 、 水 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Muraymycin Analogues Active against Anti-Drug-Resistant Bacteria

  摘要：

  Muraymycin analogues with a lipophilic substituent were synthesized using an Ugi four-component assemblage. This approach provides ready access to a range of analogues simply by altering the aldehyde component. The impact of the lipophilic substituent on the antibacterial activity was very large, and analogues 7b-e and 8b-e exhibited good activity against a range of Gram;positive bacterial pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. This study also showed that the accessory urea-dipeptide motif contributes to MraY inhibitory and antibacterial activity. The knowledge obtained from our structure activity relationship study of muraymycins provides further direction toward the design of potent MraY inhibitors. This study has set the stage for the generation of novel antibacterial "lead" compounds based on muraymycins.

  DOI：

  10.1021/ml100057z
• 作为产物：
  描述：

  tert-butyl (2S,3S)-3-[[(3aR,4S,6R,6aR)-2,2-diethyl-6-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]oxy]-3-[(3aR,4R,6R,6aR)-4-(2,4-dioxopyrimidin-1-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]-2-(3-cyanopropylamino)propanoate 、 以 乙醇 为溶剂， 反应 48.0h， 以47.6 mg的产率得到tert-butyl (2S)-2-[[(1S)-2-[[1-[3-[[(1S,2S)-1-[[(3aR,4S,6R,6aR)-2,2-diethyl-6-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]oxy]-1-[(3aR,4R,6R,6aR)-4-(2,4-dioxopyrimidin-1-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]-3-[(2-methylpropan-2-yl)oxy]-3-oxopropan-2-yl]amino]propylamino]-1-oxoheptadecan-2-yl]-[(2,4-dimethoxyphenyl)methyl]amino]-2-oxo-1-[(6S)-2-(2,2,2-trichloroethoxysulfonylamino)-1,4,5,6-tetrahydropyrimidin-6-yl]ethyl]carbamoylamino]-3-methylbutanoate
  参考文献：
  名称：

  Mechanistic Analysis of Muraymycin Analogues: A Guide to the Design of MraY Inhibitors

  摘要：

  The systematic structure activity relationship (SAX) of the muraymycins (MRYs) using an Ugi four-component reaction (U4CR) was investigated. The impact of the lipophilic substituent on antibacterial activity was significant, and the analogues 8 and 9 having a lipophilic side chain exhibited good activity against a range of Gram-positive bacterial pathogens, including MRSA and VRE. Further investigation of compounds 8 and 9 revealed these analogues to be selective inhibitors of the MraY transferase and nontoxic to HepG2 cells. The SAX of the accessory urea peptide moiety indicated that it could be simplified. Our SAX study of the MRYs suggests a probable mechanism for inhibition of the MraY, where the inner moiety of the urea dipeptide motif interacts with the carbohydrate recognition domain in the cytoplasmic loop S. The predicted binding model would provide further direction toward the design of potent MraY inhibitors. This study has set the stage for the generation of novel antibacterial "lead" compounds based on MRYs.

  DOI：

  10.1021/jm200906r