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 | 1004751-08-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 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
• 英文别名: (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)propanoic acid
• CAS: 1004751-08-9
• 化学式: C₃₇H₅₀N₄O₁₅
• 分子量: 790.822
• InChiKey: IQZZGIZKOMYWIP-WWLJHXPTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  56
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  228
• 氢给体数：
  4
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  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 、 十二烷基伯胺 在 1-羟基苯并三唑 、 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， 反应 12.0h， 以93%的产率得到6-benzyloxycarbonylamino-5-O-[5-tert-butoxycarbonylamino-5-deoxy-2,3-O-(3-pentylidene)-β-D-ribofuranosyl]-6-deoxy-N-dodecyl-2,3-O-isopropylidene-1-(uracil-1-yl)-β-D-glycero-L-talo-heptofuranuronamide
  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：

  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

文献信息

• Total Synthesis of (−)-Muraymycin D2 and Its Epimer
  作者：Tetsuya Tanino、Satoshi Ichikawa、Motoo Shiro、Akira Matsuda

  DOI：10.1021/jo9027193

  日期：2010.3.5

  desulfonylation upon acetolysis of the oxathiazinane ring to give 43 in good yield. The amine obtained by selective removal of the Cbz group of the alcohol 44 was reacted with MeSC(═O)-l-Val-O-t-Bu (38) to provide 45, which was oxidized to the carboxylic acid 46. Reaction of 46, isonitrile 51, isovaleraldehyde, and 2,4-dimethoxybenzylamine furnished the desired Ugi products, the final deprotection of which successfully

  描述了（-）-muraymycin（MRY）D2及其差向异构体（抗菌核苷天然产物）的第一个全合成的完整细节。该方法的关键战略要素包括尿素二肽部分的制备在含有所述muraymycins发现升-外延-capreomycidine经由所述氨基磺酸酯的氮宾C-H插入10通过的Ugi 4和所述完全受保护muraymycin骨架在后期阶段-组分反应。因此，将氨基磺酸盐10与10 mol％的Rh 2（esp）2催化剂的丁腈CH插入，以47％的收率得到环状氨基磺酸盐11a和11b（11a：11b= 1：2.0）。环状胍骨架的构建是通过HgBr 2促进的42的环化作用，然后在草ath嗪烷环的乙酰化作用下进行脱磺酰作用而得到的，从而以良好的收率得到43。通过选择性去除Cbz基团的醇的的得到的胺44用MESC（= O）反应-升-Val-O-吨-Bu（38），以提供45，将其氧化为羧酸46。反应46，异腈51，异戊醛和2
• Design and synthesis of diketopiperazine and acyclic analogs related to the caprazamycins and liposidomycins as potential antibacterial agents
  作者：Shinpei Hirano、Satoshi Ichikawa、Akira Matsuda

  DOI：10.1016/j.bmc.2007.09.022

  日期：2008.1

  A systematic simplification methodology of a class of 6'-N-alkyl-5'-O-aminoribosyl-glycyluridine antibiotics was shown to produce potential antibacterial agents having a novel mechanism of action. Diketopiperazines and acyclic analogs of the caprazamycins (CPZs) and liposidomycins (LPMs) were efficiently synthesized, and their antibacterial activity was evaluated. The diketopiperazine analog 11a and the acyclic analogs 12a and 16a having a palmitoyl group as a lipophilic side chain exhibited moderate antibacterial activities with MICs of 12.5-50 mu g/mL. This approach could provide ready access to a range of analogs for the development of potential antibacterial agents. (c) 2007 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.