methyl (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-(phenylmethoxycarbonylamino)propanoate | 1004751-07-8

• 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: methyl (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-(phenylmethoxycarbonylamino)propanoate
• CAS: 1004751-07-8
• 化学式: C₃₈H₅₂N₄O₁₅
• 分子量: 804.849
• InChiKey: IQVHWKNFGZIHBF-XAENXYNPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  57
• 可旋转键数：
  17
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  217
• 氢给体数：
  3
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  methyl (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-(phenylmethoxycarbonylamino)propanoate 在 barium dihydroxide 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以73%的产率得到6-benzyloxycarbonylamino-5-O-[5-tert-butoxycarbonylamino-5-deoxy-2,3-O-(3-pentylidene)-β-D-ribo-pentofuranosyl]-6-deoxy-2,3-O-isopropylidene-1-(uracil-1-yl)-β-D-glycero-L-talo-heptofuranuronate
  参考文献：
  名称：

  Synthesis of Caprazamycin Analogues and Their Structure−Activity Relationship for Antibacterial Activity

  摘要：

  Synthesis of palmitoyl caprazol 7, which possesses a simple fatty acyl side chain at the 3"'-position of the diazepanone moiety, was carried out and their antibacterial activity was evaluated. The key elements of our approach include the improved synthesis of the key 5'-p-0-aminoribosyl-glycyluridine derivative, installation of the palmitoyl side chain to the cyclization precursor, and the construction of the diazepanone by an intramolecular reductive amination. The second generation synthesis of (+)-caprazol was also established. Palmitoyl caprazol 7 exhibited antibacterial activity against Mycobacterium smegmatis ATCC607 (MIC = 6.25 mu g/mL) with potency similar to that of the caprazamycins (CPZs). Palmitoyl caprazol 7 and N-6'-desmethyl palmitoyl caprazol 28 also exhibited antibacterial activity against drug-resistant bacteria including methyciline-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) strains (MIC = 3.13-12.5 mu g/mL).

  DOI：

  10.1021/jo702264e
• 作为产物：
  描述：

  、 二碳酸二叔丁酯 生成 methyl (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-(phenylmethoxycarbonylamino)propanoate
  参考文献：
  名称：

  Function-Oriented Synthesis of Simplified Caprazamycins: Discovery of Oxazolidine-Containing Uridine Derivatives as Antibacterial Agents against Drug-Resistant Bacteria

  摘要：

  The rational simplification of the caprazamycin (CPZ) class of nucleoside natural products was carried out to address their molecular complexity. First, analogues 6-8, where the diazepanone ring of the CPZ was removed and a lipophilic side chain was attached to either the C-7' or N(6') atom, were used to investigate the conformation activity relationship. On the basis of this relationship, we designed the oxazolidine-containing uridine derivatives 18-21 by restricting the conformation of 6-8. As a result, the 'Bu ester derivatives 20 were found to be the most active against a range of bacterial strains containing VRE with a potency similar to that of the parent CPZs. This study provides a novel strategy for the development of a new type of antibacterial agent effective against drug-resistant bacteria.

  DOI：

  10.1021/jm100243n

文献信息

• Synthesis of Caprazamycin Analogues and Their Structure−Activity Relationship for Antibacterial Activity
  作者：Shinpei Hirano、Satoshi Ichikawa、Akira Matsuda

  DOI：10.1021/jo702264e

  日期：2008.1.1

  Synthesis of palmitoyl caprazol 7, which possesses a simple fatty acyl side chain at the 3"'-position of the diazepanone moiety, was carried out and their antibacterial activity was evaluated. The key elements of our approach include the improved synthesis of the key 5'-p-0-aminoribosyl-glycyluridine derivative, installation of the palmitoyl side chain to the cyclization precursor, and the construction of the diazepanone by an intramolecular reductive amination. The second generation synthesis of (+)-caprazol was also established. Palmitoyl caprazol 7 exhibited antibacterial activity against Mycobacterium smegmatis ATCC607 (MIC = 6.25 mu g/mL) with potency similar to that of the caprazamycins (CPZs). Palmitoyl caprazol 7 and N-6'-desmethyl palmitoyl caprazol 28 also exhibited antibacterial activity against drug-resistant bacteria including methyciline-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) strains (MIC = 3.13-12.5 mu g/mL).
• Function-Oriented Synthesis of Simplified Caprazamycins: Discovery of Oxazolidine-Containing Uridine Derivatives as Antibacterial Agents against Drug-Resistant Bacteria
  作者：Kensuke Ii、Satoshi Ichikawa、Bayan Al-Dabbagh、Ahmed Bouhss、Akira Matsuda

  DOI：10.1021/jm100243n

  日期：2010.5.13

  The rational simplification of the caprazamycin (CPZ) class of nucleoside natural products was carried out to address their molecular complexity. First, analogues 6-8, where the diazepanone ring of the CPZ was removed and a lipophilic side chain was attached to either the C-7' or N(6') atom, were used to investigate the conformation activity relationship. On the basis of this relationship, we designed the oxazolidine-containing uridine derivatives 18-21 by restricting the conformation of 6-8. As a result, the 'Bu ester derivatives 20 were found to be the most active against a range of bacterial strains containing VRE with a potency similar to that of the parent CPZs. This study provides a novel strategy for the development of a new type of antibacterial agent effective against drug-resistant bacteria.