5-O-desosaminyl-6-O-methylerythronolide A 9-oxime | 561327-03-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-O-desosaminyl-6-O-methylerythronolide A 9-oxime
• 英文别名: (E)-5-O-desosaminyl-6-O-methylerythronolide A 9-oxime；3-O-descladinosyl-3-hydroxyl-6-O-methylerythromycin A 9-E-oxime；decladinosyl clarithromycin (9E)-oxime；(3R,4S,5S,6R,7R,9R,10E,11S,12R,13S,14R)-6-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-4,12,13-trihydroxy-10-hydroxyimino-7-methoxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecan-2-one
• CAS: 561327-03-5
• 化学式: C₃₀H₅₆N₂O₁₀
• 分子量: 604.782
• InChiKey: BDYUTGOVLJRCQO-BHQGQJMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  42
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  171
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  5-O-desosaminyl-6-O-methylerythronolide A 9-oxime 在 吡啶 、 甲醇 、 三甲基乙酰氯 、 三乙胺 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 16.0h， 生成 pyridin-3-yl-acetic acid 10-(3-acetoxy-4-dimethylamino-6-methyl-tetrahydro-pyran-2-yloxy)-4-ethyl-14-hydroxyimino-11-methoxy-3a,7,9,11,13,15-hexamethyl-2,6-dioxo-dodecahydro-1,3,5-trioxa-cyclopentacyclotetradecen-8-yl ester
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of a Novel Series of Acylides:  3-O-(3-Pyridyl)acetylerythromycin A Derivatives

  摘要：

  A novel series of acylides, 3-O-(aryl)acetylerythromycin A derivatives, were synthesized and evaluated. These compounds have significant potent antibacterial activity against not only Gram-positive pathogens, including inducibly macrolide-lincosamide-streptogramin B (MLSB)-resistant and efflux-resistant strains, but also Gram-negative pathogens, such as H. influenzae. 6,9:11,12-Dicarbonate acylide 47 (FMA0122) was twice as active against H. influenzae than azithromycin, whereas it showed only moderate in vivo efficacy in mouse protection tests. However, the 11,12-carbamate acylide 19 (TEA0929), which showed potent antibacterial activity against almost all of the main causative pathogens of community-acquired pneumonia tested, exhibited excellent in vivo efficacy comparable to those of second-generation macrolides.

  DOI：

  10.1021/jm020568d
• 作为产物：
  描述：

  克拉霉素 在 盐酸 、 盐酸羟胺 、 sodium acetate 作用下， 以 水 为溶剂， 生成 5-O-desosaminyl-6-O-methylerythronolide A 9-oxime
  参考文献：
  名称：

  Synthesis and antibacterial activity of novel modified 5-O-mycaminose 14-membered ketolides

  摘要：

  A practicable method of introducing a side chain to the C-4' position of 5-O-desosamine in the 14membered ketolides was developed. And using this method, a series of novel modified 5-O-mycaminose ketolides were synthesized. These ketolides containing 5-O-4'-carbamate mycaminose were evaluated for their in vitro antibacterial activities against some respiratory pathogens. 15b and 18e showed comparable activity to telithromycin and clarithromycin. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.08.023

文献信息

• Synthesis and Antibacterial Activity of Acylides (3-<i>O</i>-Acyl-erythromycin Derivatives):  A Novel Class of Macrolide Antibiotics
  作者：Tetsuya Tanikawa、Toshifumi Asaka、Masato Kashimura、Yoko Misawa、Keiko Suzuki、Masakazu Sato、Kazuya Kameo、Shigeo Morimoto、Atsushi Nishida

  DOI：10.1021/jm015566s

  日期：2001.11.1

  Introduction of an acyl group to the 3-O-position of erythromycin A derivatives instead of L-cladinose led to a novel class of macrolide antibiotics that we named "acylides". The 3-O-nitrophenylacetyl derivative TEA0777 showed significantly potent activity against not only erythromycin-susceptible Gram-positive pathogens but also inducibly macrolides-lincosamides-streptogramin B (MLS(B))-resistant

  将酰基引入红霉素A衍生物而不是L-cladinose的3-O-位导致了一类新的大环内酯类抗生素，我们将其命名为“酰化物”。3-O-硝基苯基乙酰基衍生物TEA0777不仅对易感红霉素的革兰氏阳性病原体而且对可诱导大环内酯类，林可酰胺类，链霉菌素B（MLS（B））的金黄色葡萄球菌和对外排毒的肺炎链球菌均显示出显着的有效活性。这些结果表明酰化物具有作为下一代大环内酯类抗生素的潜力。
• 10.1016/j.bioorg.2024.107712
  作者：Zhang, Na、Liu, Wen-Tian、Cui, Xin-Yi、Liu, Si-Meng、Ma, Cong-Xuan、Liang, Jian-Hua

  DOI：10.1016/j.bioorg.2024.107712

  日期：——

  strains of and , which are typically refractory to existing C-3 modified macrolides. Notably, hybrid (coded ZN-51) represented a pioneering class of agents distinguished by its dual modes of action, with ribosomes as the primary target and topoisomerases as the secondary target. As a novel chemotype of macrolide-quinolone hybrids, alkylide is a valuable addition to our armamentarium against macrolide-resistant

  TE-802 等酮内酯（3-酮）和 TEA0929 等酰基（3--酰基）对含有红霉素核糖体甲基化 () 基因的组成型抗性病原体无效。继我们之前对烷基化物（3--烷基）的研究之后，我们探索了将 (R/S) 3-descladinosyl erythromycin 与 6/7-quinolone 基序相结合的杂化物的构效关系，该杂化物具有扩展的醚连接间隔基，重点是其对具有组成型基因抗性的病原体的功效。优化的化合物不仅恢复了对诱导抗性病原体的功效，而且还表现出显着增强的对 和 的组成型抗性菌株的活性，这些菌株通常对现有的 C-3 修饰大环内酯类耐药。值得注意的是，hybrid（编码为 ZN-51）代表了一类开创性的药物，以其双重作用模式而著称，以核糖体为主要目标，拓扑异构酶为次要目标。作为大环内酯-喹诺酮杂合体的新型化学型，烷基化物是我们对抗大环内酯耐药细菌的宝贵补充。
• Structure–activity relationships of novel alkylides: 3-O-Arylalkyl clarithromycin derivatives with improved antibacterial activities
  作者：Jian-Hua Liang、Xiao-Li Li、He Wang、Kun An、Yue-Ying Wang、Ying-Chun Xu、Guo-Wei Yao

  DOI：10.1016/j.ejmech.2012.01.023

  日期：2012.3

  A series of novel alkylides, possessing 3-O-arylallcyl group instead of 3-O-cladinose, were designed, synthesized and evaluated for in vitro antibacterial activities. The increased potency clearly ranked by the order of 3-O-(3-aryl-2-propargyl), 3-O-(3-aryl-E-prop-2-enyl), 3-O-(3-aryl-propyl), and 3-O-(3-aryl-Z-prop-1-enyl) groups. Some alkylides, exemplified by 7a, 10a, 21, 22, 26, 27 and 33, showed improved activities against inducible MLSB resistance and efflux resistance compared to the second-generation macrolides. Among them, 26 possessed comparable activities against erythromycin-susceptible Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes (MICs of 0.016-0.5 mu g/mL). Moreover, 26 displayed dramatically enhanced potency against both efflux resistant and inducibly MLSB resistant strains (MICs of 0.125-0.5 mu g/mL) resistant to clarithromycin and azithromycin (MICs of 1 >254 mu g/mL), independent of methicillin-susceptible and methicillin-resistant phenotypes. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Synthesis, antibacterial activity and docking of 14-membered 9-O-(3-arylalkyl) oxime 11,12-cyclic carbonate ketolides
  作者：Jian-Hua Liang、Kun An、Wei Lv、Mark Cushman、He Wang、Ying-Chun Xu

  DOI：10.1016/j.ejmech.2012.10.054

  日期：2013.1

  A series of 9-O-(3-aryl-2-propargyl)oxime ketolides 8 was synthesized and evaluated for in vitro antibacterial activity. Among 8, 8b-8d, and 8h-8l displayed dramatically improved potency against inducibly MLSB-resistant and efflux-resistant pathogens as compared to clarithromycin and azithromycin. Especially, 8i (Ar=4-isoquinolyl) possessed an MIC of 0.064 mu g/mL against constitutively MLSB-resistant Streptococcus pneumoniae, and MICs of 0.032-0.064 mu g/mL against methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus hominis. The analog 10 with a propyl linker was less effective than both the corresponding 8 and 9 containing propynyl and propenyl linkers. A docking study was performed to gain insight into the binding mode of series 8 and 9 and to rationalize the disparity found in the SAR of 8 and 9. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Synthesis and antibacterial activity of novel modified 5-O-mycaminose 14-membered ketolides
  作者：Yanpeng Xu、Xiaozhuo Chen、Di Zhu、Yi Liu、Zhehui Zhao、Longlong Jin、Chao Liu、Pingsheng Lei

  DOI：10.1016/j.ejmech.2013.08.023

  日期：2013.11

  A practicable method of introducing a side chain to the C-4' position of 5-O-desosamine in the 14membered ketolides was developed. And using this method, a series of novel modified 5-O-mycaminose ketolides were synthesized. These ketolides containing 5-O-4'-carbamate mycaminose were evaluated for their in vitro antibacterial activities against some respiratory pathogens. 15b and 18e showed comparable activity to telithromycin and clarithromycin. (C) 2013 Elsevier Masson SAS. All rights reserved.