(2S,3R,4S,6R)-4-(dimethylamino)-2-(((3R,5R,6R,7R,9R,13S,14R,E)-14-ethyl-13-hydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,4,10-trioxooxacyclotetradec-11-en-6-yl)oxy)-6-methyltetrahydro-2H-pyran-3-yl acetate | 214694-76-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,3R,4S,6R)-4-(dimethylamino)-2-(((3R,5R,6R,7R,9R,13S,14R,E)-14-ethyl-13-hydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,4,10-trioxooxacyclotetradec-11-en-6-yl)oxy)-6-methyltetrahydro-2H-pyran-3-yl acetate
• 英文别名: 2'-O-acetyl-10,11-didehydro-11-deoxy-3-O-descladinosyl-3-oxo-6-O-methyl-erythromycin A；11-deoxy-10,11-didehydro-3-de[(2,6-dideoxy-3C-methyl-3O-methyl-α-L-ribohexopyranosyl)oxy]-6O-methyl-3-oxoerythromycin-2'-acetate；(10E)-2'-O-acetyl-3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)oxy]-10,11-didehydro-11-deoxy-6-O-methyl-3-oxoerythromycin；[(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(3R,5R,6R,7R,9R,11E,13S,14R)-14-ethyl-13-hydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,4,10-trioxo-1-oxacyclotetradec-11-en-6-yl]oxy]-6-methyloxan-3-yl] acetate
• CAS: 214694-76-5
• 化学式: C₃₂H₅₃NO₁₀
• 分子量: 611.774
• InChiKey: SOJIUBGHLPEDMW-SWYKMVQDSA-N

物化性质

• 熔点：
  218-219 °C
• 沸点：
  707.7±60.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  43
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  138
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (2S,3R,4S,6R)-4-(dimethylamino)-2-(((3R,5R,6R,7R,9R,13S,14R,E)-14-ethyl-13-hydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,4,10-trioxooxacyclotetradec-11-en-6-yl)oxy)-6-methyltetrahydro-2H-pyran-3-yl acetate 在 甲醇 、 sodium hydride 作用下， 以 水 、 乙腈 为溶剂， 反应 21.0h， 生成
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of Ketolides (6-O-Methyl-3-oxoerythromycin Derivatives):  A New Class of Antibacterials Highly Potent Against Macrolide-Resistant and -Susceptible Respiratory Pathogens

  摘要：

  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.

  DOI：

  10.1021/jm980240d
• 作为产物：
  描述：

  克拉红霉素EP杂质I 在 吡啶 、 三氟乙酸吡啶 、 potassium carbonate 、 二甲基亚砜 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 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 、 丙酮 为溶剂， 反应 49.0h， 生成 (2S,3R,4S,6R)-4-(dimethylamino)-2-(((3R,5R,6R,7R,9R,13S,14R,E)-14-ethyl-13-hydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,4,10-trioxooxacyclotetradec-11-en-6-yl)oxy)-6-methyltetrahydro-2H-pyran-3-yl acetate
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of Ketolides (6-O-Methyl-3-oxoerythromycin Derivatives):  A New Class of Antibacterials Highly Potent Against Macrolide-Resistant and -Susceptible Respiratory Pathogens

  摘要：

  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.

  DOI：

  10.1021/jm980240d

文献信息

• Synthesis of novel macrolide derivatives with imidazo[4,5-b]pyridinyl sulfur contained alkyl side chains and their antibacterial activity
  作者：Peng Xu、Lu Liu、Xiao-zhuo Chen、Yun Li、Jian Liu、Zhi-ping Jin、Guang-qiang Wang、Ping-sheng Lei

  DOI：10.1016/j.bmcl.2009.06.023

  日期：2009.8

  In an effort to find new antibiotics, a novel series of 14-membered macrolides with imidazo[4,5-b]pyridinyl sulfur contained alkyl side chains has been synthesized based on commercially available clarithromycin. Chemical transformation of hydroxy group at position C-3 afforded range of ketolides and acylides. Compared to telithromycin, compound 15a demonstrated improved in vitro activity against e

  为了寻找新的抗生素，已经基于市售的克拉霉素合成了一系列新的具有咪唑并[4，5- b ]吡啶基硫烷基侧链的14元大环内酯类化合物。在C-3位上的羟基的化学转化提供了酮醇化物和酰化物的范围。与替利霉素相比，化合物15a表现出对红霉素敏感和耐药菌株的体外活性提高。
• [EN] NEW MACROLIDES AND THEIR USE<br/>[FR] NOUVEAUX MACROLIDES ET LEUR UTILISATION
  申请人：BASILEA PHARMACEUTICA AG

  公开号：WO2011018510A1

  公开（公告）日：2011-02-17

  The invention relates to macrolide compounds of formula (I), the use of said compounds as medicaments, in particular for the treatment or prevention of inflammatory and allergic diseases, pharmaceutical compositions containing said compounds and to processes for their preparation. The invention relates in particular to macrolide compounds with antiinflammatory activity mediated primarily through inhibition of phosphodiesterase 4 (PDE4) which makes them useful for the treatment and/or prevention of inflammatory and allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rheumatoid arthritis, atopic dermatitis or inflammatory bowel disease or proliferative diseases such as cancer.

  该发明涉及公式（I）的大环内酯化合物，所述化合物的用途为药物，特别用于治疗或预防炎症和过敏性疾病，含有该化合物的药物组合物以及其制备方法。该发明特别涉及具有抗炎活性的大环内酯化合物，主要通过磷酸二酯酶4（PDE4）的抑制介导，使其在治疗和/或预防慢性阻塞性肺疾病（COPD）、哮喘、类风湿关节炎、特应性皮炎或炎症性肠病等炎症和过敏性疾病，以及癌症等增殖性疾病方面具有用途。
• 2-halogenated derivatives of 5-0 desosaminyl-erythronolide A, their preparation process and their antibiotic use
  申请人：Aventis Pharma S.A.

  公开号：US06352983B1

  公开（公告）日：2002-03-05

  Novel compounds of the formula wherein the substituents are defined as in the application having antibiotic properties.

  该式中的新化合物具有抗生素性质，其中取代基的定义如申请中所述。
• An Approach to Modify 14-Membered Lactone Macrolide Antibiotic Scaffolds
  作者：Anna Janas、Krystian Pyta、Maria Gdaniec、Piotr Przybylski

  DOI：10.1021/acs.joc.1c02799

  日期：2022.3.4

  A ketolide derivative with (12R)-configuration was obtained via a novel ketene acetal in acidic conditions. The structure of this atypical β-keto ketene acetal intermediate within the macrocyclic system has been determined by NMR and X-ray methods. The use of basic conditions at an elevated temperature yielded new, doubly α,β-unsaturated ketone macrolide derivatives with (4E)-configuration as two conformational

  通过一种新型乙烯酮缩醛在酸性条件下获得了具有 (12 R ) 构型的酮内酯衍生物。大环体系中这种非典型的 β-酮烯酮缩醛中间体的结构已通过 NMR 和 X 射线方法确定。在高温下使用碱性条件产生了新的双 α,β-不饱和酮大环内酯衍生物，具有 (4 E )-构型作为折叠或折叠构象的两种构象异构体。
• [EN] PROCESS FOR THE PRODUCTION OF TELITHROMYCIN<br/>[FR] PROCÉDÉ DE FABRICATION DE TÉLITHROMYCINE
  申请人：SANDOZ AG

  公开号：WO2009053259A1

  公开（公告）日：2009-04-30

  The present invention relates to a process for the preparation of erythromysin derivatives, in particular telithromycin of formula (I) and its pharmaceutically acceptable salts, providing the isolated intermediates in crystalline form of superior stability and purity.

  本发明涉及一种制备红霉素衍生物的方法，特别是制备式(I)的特利霉素及其药学上可接受的盐，提供具有卓越稳定性和纯度的晶体中间体。