6-O-methylerythromycin A 9-oxime | 103450-87-9

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-O-methylerythromycin A 9-oxime
• 英文别名: 3-O-descladinosyl-9-oxime clarithromycin；6-O-methylerythromycin A oxime；(3R,4S,5S,6R,7R,9R,11S,12R,13S,14R)-6-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-12,13-dihydroxy-10-hydroxyimino-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-7-methoxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecan-2-one
• CAS: 103450-87-9
• 化学式: C₃₈H₇₀N₂O₁₃
• 分子量: 762.979
• InChiKey: MWBJRTBANFUBOX-KCBOHYOISA-N

物化性质

• 熔点：
  169-171 °C
• 沸点：
  827.7±65.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  53.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  198.43
• 氢给体数：
  5.0
• 氢受体数：
  15.0

反应信息

• 作为反应物：
  描述：

  6-O-methylerythromycin A 9-oxime 在 乙酸铵 、 水 、 三氯化钛 作用下， 以 甲醇 为溶剂， 反应 6.0h， 生成 克拉霉素
  参考文献：
  名称：

  Davies, J. Sydney; Hunt, Eric; Zomaya, Iskander I., Journal of the Chemical Society. Perkin transactions I, 1990, # 5, p. 1409 - 1414

  摘要：

  DOI：
• 作为产物：
  描述：

  克拉霉素 在 盐酸羟胺 、 sodium acetate 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 17.0h， 以90%的产率得到6-O-methylerythromycin A 9-oxime
  参考文献：
  名称：

  合成的和新颖的抗菌活性3- ö -arylalkylcarbamoyl -3- ö -descladinosyl -9- Ö - （2-氯苄基）肟衍生物的克拉霉素

  摘要：

  一种新型系列3- ö -arylalkylcarbamoyl -3- ö -descladinosyl -9- ø -克拉霉素衍生物（2-氯苄基）肟，设计，合成并评价了它们的体外抗菌活性。发现这些衍生物对易感和抗性细菌菌株具有很强的活性。其中，化合物7a和7q对表达mef A基因的耐红霉素的肺炎链球菌具有最强的活性（0.125 µg / mL）。此外，化合物7f，7i，7p和7z的抗青霉素活性显着提高（4 µg / mL）金黄色葡萄球菌ATCC31007以及化合物7a，7b，7f，7p和7z对耐红霉素的化脓性链球菌显示了更高的活性（8 µg / mL）。特别地，化合物7z对测试的药物敏感性和抗性细菌菌株表现出有效和平衡的活性。

  DOI：

  10.1016/j.bmcl.2018.09.012

文献信息

• 3-Keto-9-O-substituted Oxime Derivatives of 6-O-Methyl Erythromycin A Synthesis and In Vitro Activity.
  作者：CHEN SHENGXI、XU XIANDONG、YU LANXIANG

  DOI：10.7164/antibiotics.54.506

  日期：——

  A series of 3-keto-9-O-substituted oxime derivatives of 6-O-methyl erythromycin A were prepared with a novel synthetic route, which include 6 reaction steps--oximation, protection, hydrolysis, oxidation, deprotection and addition. The antibacterial activity of these compounds were tested in vitro against both erythromycin-susceptible and erythromycin-resistant organisms. Several of these derivatives

  以新颖的合成路线制备了一系列6-O-甲基红霉素A的3-酮-9-O-取代的肟衍生物，包括6个反应步骤：肟化，保护，水解，氧化，脱保护和加成。在体外测试了这些化合物对红霉素敏感和抗红霉素的细菌的抗菌活性。与红霉素A相比，这些衍生物中的几种显示出对某些抗红霉素生物的抗菌活性得到改善。
• [EN] PROCESS FOR THE PREPARATION OF 6-O-METHYLERYTHROMYCIN A 9-OXIME<br/>[FR] PROCÉDÉ DE PRÉPARATION DE 9-OXIME DE 6-O-MÉTHYLÉRYTHROMYCINE A
  申请人：ALEMBIC LTD

  公开号：WO2009007988A1

  公开（公告）日：2009-01-15

  The present invention relates to process for the preparation of 6-O-methylerythromycin A 9-oxime by treating 6-O-methylerythromycin A with hydroxyl amine hydrochloride in the presence of a base and a solvent.

  本发明涉及一种制备6-O-甲氧基红霉素A 9-肟的方法，通过在碱和溶剂的存在下，用羟胺盐酸盐处理6-O-甲氧基红霉素A。
• Structure-Activity Relationship Study of 6-O-Methylerythromycin 9-O-Substituted Oxime Derivatives.
  作者：Yutaka KAWASHIMA、Yuki YAMADA、Toshifumi ASAKA、Yoko MISAWA、Masato KASHIMURA、Sigeo MORIMOTO、Takeo ONO、Takatoshi NAGATE、Katsuo HATAYAMA、Shuichi HIRONO、Ikuo MORIGUCHI

  DOI：10.1248/cpb.42.1088

  日期：——

  In order to develop new-generation macrolide antibiotics active against erythromycin (EM)-resistant strains, a series of 6-O-methyl EM 9-O-substituted oxime derivatives was synthesized and evaluated for antibacterial activity against EM-resistant (S. aureus J-109) and susceptible (S. aureus 209P) strains. To understand how substituents affect the biological activity, the quantitative structure-activity relationships (QSAR) was analyzed using the Hansch-Fujita method. With the EM-resistant strain, the positive coefficient for log P may indicate that higher hydrophobicity of molecules is favorable for antibacterial activity. The negative coefficients of the Sterimol parameters L, B1, and B5 may indicate that long, bulky substituents are unfavorable. With the EM-susceptible strain, the negative coefficient for log P may indicate that hydrophilicity is important for antibacterial activity. A short substituent is also required to improve the activity. Based on the QSAR model, a derivative (87) having an anthracenylmethyl moiety was synthesized to reinforce and confirm the correlation. The activity of 87 against the EM-resistant strain was significant. In QSARs of 6-O-methyl EM-A 9-O-substituted oxime derivatives, the difference of the contribution of log P to the antibacterial activity between EM-resistant and susceptible strains was clearly recognized.

  为了开发对红霉素（EM）耐药菌株有活性的新一代大环内酯类抗生素，合成了一系列 6-O 甲基 EM 9-O 取代肟衍生物，并评估了它们对 EM 耐药菌株（金黄色葡萄球菌 J-109）和易感菌株（金黄色葡萄球菌 209P）的抗菌活性。为了了解取代基对生物活性的影响，采用 Hansch-Fujita 方法分析了定量结构-活性关系（QSAR）。对于抗 EM 菌株，log P 的正系数可能表明分子的疏水性越高，抗菌活性越强。Sterimol参数L、B1和B5的负系数可能表明，长而笨重的取代基不利于抗菌。对于 EM 易感菌株，log P 的负系数可能表明亲水性对抗菌活性很重要。要提高活性，还需要短取代基。根据 QSAR 模型，合成了一种具有蒽甲基的衍生物 (87)，以加强和确认相关性。87 对 EM 抗性菌株具有显著的活性。在 6-O- 甲基 EM-A 9-O 取代肟衍生物的 QSAR 中，抗 EM 菌株和易感菌株之间抗菌活性的对数 P 贡献率的差异得到了清楚的认识。
• WO2006/50942
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis and Antibacterial Activity of Ketolides (6-<i>O</i>-Methyl-3-oxoerythromycin Derivatives):  A New Class of Antibacterials Highly Potent Against Macrolide-Resistant and -Susceptible Respiratory Pathogens
  作者：Constantin Agouridas、Alexis Denis、Jean-Michel Auger、Yannick Benedetti、Alain Bonnefoy、François Bretin、Jean-François Chantot、Arlette Dussarat、Claude Fromentin、Solange Gouin D'Ambrières、Sylvette Lachaud、Patrick Laurin、Odile Le Martret、Véronique Loyau、Nicole Tessot

  DOI：10.1021/jm980240d

  日期：1998.10.1

  In the search for new antibiotics active against macrolide-resistant pneumococci and Haemophilus influenzae, we synthesized a new class of 3-oxo-6-O-methylerythromycin derivatives, so-called "ketolides". A keto function was introduced in position 3 after removal of L-cladinose, a sugar which has long been thought essential. Further modifications of the macrolactone backbone allowed us to obtain three different series of 9-oxime, 11,12-carbamate, and 11,12-hydrazonocarbamate ketolides. These compounds were found to be very active against penicillin/erythromycin-resistant pneumococci and noninducers of MLS(B) resistance. The 11,12-substituted ketolide 61 (HMR 3004) demonstrated a potent activity against multiresistant pneumococci associated with a well-balanced activity against all bacteria involved in respiratory infections including H. influenzae, Mycoplasma catarrhalis, group A streptococci, and atypical bacteria. In addition HMR 3004 displayed high therapeutic activity in animals infected by all major strains, irrespective of their resistance phenotype.