3-hydroxy-6-O-methyl-10,11-anhydroerythromycin A | 208456-82-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-hydroxy-6-O-methyl-10,11-anhydroerythromycin A
• 英文别名: 3-OH-6-O-methyl-10,11-anhydro-erythromycin A；10,11-anhydro-6-O-methyl-descladinosyl-erythromycin A
• CAS: 208456-82-0
• 化学式: C₃₀H₅₃NO₉
• 分子量: 571.752
• InChiKey: GVPDZXPAAWSLFA-FNPLNPRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.46
• 重原子数：
  40.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  134.99
• 氢给体数：
  3.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  3-hydroxy-6-O-methyl-10,11-anhydroerythromycin A 在 双氧水 作用下， 以 甲醇 、 水 为溶剂， 反应 5.0h， 以68%的产率得到10,11-anhydro-6-O-methyl-descladinosyl-erythromycin A N-oxide
  参考文献：
  名称：

  [EN] 10-SUBSTITUTED MACROLIDE ANTIBIOTICS
  [FR] MACROLIDES

  摘要：

  公开号：

  WO2004056843A3
• 作为产物：
  描述：

  2’-O-acetyl-3-O-decladinosyl-clarithromycin 在 吡啶 、 甲醇 、 potassium tert-butylate 、 3-溴丙烯 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 9.5h， 生成 3-hydroxy-6-O-methyl-10,11-anhydroerythromycin A
  参考文献：
  名称：

  Synthesis and antibacterial activity of 2, 3-dehydro-3-O-(3-aryl-E-prop-2-enyl)-10, 11-anhydroclarithromycin derivatives

  摘要：

  在 allyl 溴化物和 KOtBu 存在下，一级基团被连接到酮类化合物的 3-酮功能上。因此，在盐酸钯(II)和三(o-托烯)磷的存在下，得到的 2, 3-脱氢-3-O-allyl-10, 11-anhydroclarithromycin 衍生物进行 Heck 反应，生成了 3-O-(3-芳基-E-丙-2-烯基)侧链，而非之前报道的 3-O-(3-芳基-Z-丙-1-烯基)侧链。结果表明，β-氢消除中的一些立体因素可能调控异构化。2, 3-脱氢-3-O-(3-芳基-E-丙-2-烯基)-10, 11-anhydroclarithromycin 衍生物的活性较低。

  DOI：

  10.1038/ja.2011.11

文献信息

• Synthesis and antibacterial activities of a novel alkylide: 3-O-(3-aryl-2-propargyl) and 3-O-(3-aryl-2-propenyl)clarithromycin derivatives
  作者：Jian-Hua Liang、Yue-Ying Wang、He Wang、Xiao-Li Li、Kun An、Ying-Chun Xu、Guo-Wei Yao

  DOI：10.1016/j.bmcl.2010.03.038

  日期：2010.5

  A series of novel 3-O-(3-aryl-E-2-propenyl)clarithromycin derivatives 8 and 3-O-(3-aryl-2-propargyl)clarithromycin derivatives 11 were designed, synthesized, and evaluated for their in vitro antibacterial activities. Compared with 8c and 11c (Ar was 5-pyrimidyl), 3-O-(3-(5′-pyrimidyl)-Z-1-propenyl) counterpart 6c displayed 4- to 64-fold more potent activities against erythromycin-susceptible Staphylococcus

  设计，合成并评价了一系列新颖的3- O-（3-芳基-E -2-丙烯基）克拉霉素衍生物8和3- O-（3-芳基-2-炔丙基）克拉霉素衍生物11抗菌活性。与8c和11c（Ar是5-pyrimidyl）相比，3- O-（3-（5'-pyrimidyl）-Z -1-丙烯基）对应物6c对红霉素敏感的葡萄球菌的有效活性高4到64倍金黄色葡萄球菌和肺炎链球菌。此外，6c，8c的活动通常，抗红霉素的金黄色葡萄球菌和肺炎链球菌的11c和11c比参考化合物克拉霉素和阿奇霉素高4倍。
• Introduction of a nitrogen-containing side chain appended on C-10 of cethromycin leads to reduced CYP3A4 inhibition (WO2014049356A1)
  作者：Jian-Hua Liang

  DOI：10.1517/13543776.2014.971754

  日期：2015.1.2

  Introduction: Infections caused by antibiotic-resistant bacteria pose an increasing risk for clinical treatment. Macrolide-lincosamide-streptogramin B is becoming increasingly ineffective due to the methylation at the binding site of bacteria. Despite great efforts on the natural product, erythromycin, only one derivative, that is, telithromycin, capable of fighting against resistant bacteria has so far been marketed. However, the 3'-dimethylamino group is readily metabolized to a nitroso group, which would inhibit CYP3A4, a very important metabolic enzyme responsible for nearly half of all marketed drugs.Areas covered: Modifications at C-10 of erythromycin were seldom reported. This invention disclosed novel ketolides that had a side chain comprising additional nitrogen atoms in place of the original 10-methyl group. Surprisingly, introduction of the side chain at C-10 led to reduced cytochrome inhibition and increased metabolic stability. As a result, the limited ability to inhibit CYP3A4 would relieve the drug-drug interaction and improve the safety of drug co-administration.Expert opinion: This invention opens a new avenue for future modifications to the erythromycin family. It remains unclear how the side chain effected on reduction of CYP inhibition. To fully identify structure-activity relationships, the MIC data of the derivatives on gram-negative bacteria is desirable.