methyl (2S,3S)-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]-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoate | 935560-16-0

• 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,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-hydroxy-2-(phenylmethoxycarbonylamino)propanoate
• CAS: 935560-16-0
• 化学式: C₂₃H₂₇N₃O₁₀
• 分子量: 505.481
• InChiKey: JPNNUKIQUYYQSD-GRUVHVDGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  162
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  methyl (2S,3S)-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]-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoate 在 三氟乙酸 作用下， 以 水 为溶剂， 反应 1.0h， 生成
  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
• 作为产物：
  描述：

  2’,3’邻异亚丙基尿苷 在 次氯酸叔丁酯 、 sodium hydroxide 、 2-碘酰基苯甲酸 作用下， 以 水 、 异丙醇 、 乙腈 为溶剂， 反应 8.17h， 生成 methyl (2S,3S)-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]-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoate
  参考文献：
  名称：

  Muraymycin生物合成过程中的自抗性：具有相同修饰位点和不同时间顺序的互补核苷酸转移酶和磷酸转移酶。

  摘要：

  莫来霉素是来自链霉菌属（Streptomyces spp）的抗菌天然产物。抑制涉及细胞壁生物合成的转位酶I（MraY）。在结构上，穆雷霉素由5'-C-甘氨酰尿苷（GlyU）附加在5“-氨基-5”-脱氧核糖（ADR）上形成的二糖核心，该核心存在于MraY的几种肽基核苷抑制剂中。对于穆雷霉素，GlyU-ADR二糖进一步用氨基丙基连接的肽修饰以产生最简单的结构，标注为穆雷霉素D系列。在穆雷霉素生物合成基因簇中编码的两种酶，Mur29和Mur28，在体外功能上分别为Mg·ATP依赖性核苷酸转移酶和Mg·ATP依赖性磷酸转移酶，均修饰了二糖的3″ -OH。生化特征表明，两种酶都可以利用几种核苷酸供体作为共底物，而受体底物穆来霉素也起抑制剂的作用。单底物动力学分析表明，Mur28优先磷酸化合成的GlyU-ADR二糖（一种假定的穆雷霉素的生物合成前体），而Mur29优先腺苷酸化D系列的穆雷霉素。与相应的

  DOI：

  10.1128/aac.00193-18

文献信息

• Structure–activity relationship of truncated analogs of caprazamycins as potential anti-tuberculosis agents
  作者：Shinpei Hirano、Satoshi Ichikawa、Akira Matsuda

  DOI：10.1016/j.bmc.2008.03.020

  日期：2008.5

  Systematic structure-activity relationship studies of caprazamycin (CPZ) analogs, including the aminoribose-truncated 5 and the uridine-truncated 6, have been carried out. Both 5 and 6 were synthesized efficiently via diazepanone ring construction by intramolecular reductive alkylation of aminoaldehyde derivatives. The antibacterial activity of a range of analogs, including 5 and 6, against Mycobacteriumosis was evaluated, and it was found that the uridine, the aminoribose, and the fatty acyl side chains are crucial for antibacterial activity. This study would be a guide for designing novel anti-tuberculosis agents based on the 6'-N-alkyl-5'-beta-O-aminoribosyl-glycyluridine class of antibiotics including the CPZs. (C) 2008 Elsevier Ltd. All rights reserved.
• 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.
• Self-Resistance during Muraymycin Biosynthesis: a Complementary Nucleotidyltransferase and Phosphotransferase with Identical Modification Sites and Distinct Temporal Order
  作者：Zheng Cui、Xia-Chang Wang、Xiaodong Liu、Anke Lemke、Stefan Koppermann、Christian Ducho、Jürgen Rohr、Jon S. Thorson、Steven G. Van Lanen

  DOI：10.1128/aac.00193-18

  日期：2018.7

  products from Streptomyces spp. that inhibit translocase I (MraY), which is involved in cell wall biosynthesis. Structurally, muraymycins consist of a 5'-C-glycyluridine (GlyU) appended to a 5″-amino-5″-deoxyribose (ADR), forming a disaccharide core that is found in several peptidyl nucleoside inhibitors of MraY. For muraymycins, the GlyU-ADR disaccharide is further modified with an aminopropyl-linked peptide

  莫来霉素是来自链霉菌属（Streptomyces spp）的抗菌天然产物。抑制涉及细胞壁生物合成的转位酶I（MraY）。在结构上，穆雷霉素由5'-C-甘氨酰尿苷（GlyU）附加在5“-氨基-5”-脱氧核糖（ADR）上形成的二糖核心，该核心存在于MraY的几种肽基核苷抑制剂中。对于穆雷霉素，GlyU-ADR二糖进一步用氨基丙基连接的肽修饰以产生最简单的结构，标注为穆雷霉素D系列。在穆雷霉素生物合成基因簇中编码的两种酶，Mur29和Mur28，在体外功能上分别为Mg·ATP依赖性核苷酸转移酶和Mg·ATP依赖性磷酸转移酶，均修饰了二糖的3″ -OH。生化特征表明，两种酶都可以利用几种核苷酸供体作为共底物，而受体底物穆来霉素也起抑制剂的作用。单底物动力学分析表明，Mur28优先磷酸化合成的GlyU-ADR二糖（一种假定的穆雷霉素的生物合成前体），而Mur29优先腺苷酸化D系列的穆雷霉素。与相应的