5-O-desosaminyl-3-O-phenylacetyl-6-O-methylerythronolide A

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-O-desosaminyl-3-O-phenylacetyl-6-O-methylerythronolide A
• 英文别名: 3-O-phenylacetyl-5-O-desosaminyl-6-O-methylerythronolide A；[(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-6-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-12,13-dihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,10-dioxo-oxacyclotetradec-4-yl] 2-phenylacetate
• 化学式: C₃₈H₆₁NO₁₁
• 分子量: 707.902
• InChiKey: UBSIAGGMQSLQLX-ZYSABJRQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  50
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  161
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  克拉霉素 在 盐酸 、 4-二甲氨基吡啶 作用下， 以 吡啶 、 甲醇 、 水 、 丙酮 为溶剂， 反应 37.0h， 生成 5-O-desosaminyl-3-O-phenylacetyl-6-O-methylerythronolide A
  参考文献：
  名称：

  酰化物（3-O-酰基-红霉素衍生物）的合成和抗菌活性：一类新的大环内酯类抗生素。

  摘要：

  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。

  DOI：

  10.1021/jm015566s

文献信息

• Rational prioritization strategy allows the design of macrolide derivatives that overcome antibiotic resistance
  作者：Gerhard König、Pandian Sokkar、Niclas Pryk、Sascha Heinrich、David Möller、Giuseppe Cimicata、Donna Matzov、Pascal Dietze、Walter Thiel、Anat Bashan、Julia Elisabeth Bandow、Johannes Zuegg、Ada Yonath、Frank Schulz、Elsa Sanchez-Garcia

  DOI：10.1073/pnas.2113632118

  日期：2021.11.16

  pathogens. Computational approaches are essential tools to this end since their application enables fast and early strategical decisions in the drug development process. We present a rational design approach, in which acylide antibiotics were screened based on computational predictions of solubility, membrane permeability, and binding affinity toward the ribosome. To assess our design strategy, we tested

  抗生素耐药性是对全球健康的主要威胁；这个问题可以通过开发新的抗菌剂来解决，以跟上病原体的进化适应。计算方法是实现这一目标的重要工具，因为它们的应用可以在药物开发过程中实现快速和早期的战略决策。我们提出了一种合理的设计方法，其中基于溶解度、膜渗透性和对核糖体的结合亲和力的计算预测来筛选酰基抗生素。为了评估我们的设计策略，我们测试了所有候选物的体外抑制活性，然后用几种抗生素抗性菌株在体内评估它们以确定最小抑制浓度。预测的最佳候选综合起来更容易获得，表现出更高的溶解度和对核糖体的结合亲和力，对耐药病原体的活性比泰利霉素高 56 倍。值得注意的是，我们设计的最好的化合物显示出活性，尤其是当与膜弱化药物粘菌素结合时，鲍曼不动杆菌、铜绿假单胞菌和大肠杆菌是世界卫生组织优先病原体清单中的三个最关键的目标。
• Synthesis and Antibacterial Activity of a Novel Series of Acylides:  3-<i>O</i>-(3-Pyridyl)acetylerythromycin A Derivatives
  作者：Tetsuya Tanikawa、Toshifumi Asaka、Masato Kashimura、Keiko Suzuki、Hiroyuki Sugiyama、Masakazu Sato、Kazuya Kameo、Shigeo Morimoto、Atsushi Nishida

  DOI：10.1021/jm020568d

  日期：2003.6.1

  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.
• 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。