11-N-(4-azido-butyl)-6-O-methyl-5-O-desosaminyl-3-oxo-erythronolide A 11,12-carbamate | 849407-75-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 11-N-(4-azido-butyl)-6-O-methyl-5-O-desosaminyl-3-oxo-erythronolide A 11,12-carbamate
• 英文别名: (1S,2R,5R,7R,8R,9R,11R,13R,14R)-15-(4-azidobutyl)-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-3,17-dioxa-15-azabicyclo[12.3.0]heptadecane-4,6,12,16-tetrone
• CAS: 849407-75-6
• 化学式: C₃₅H₅₉N₅O₁₀
• 分子量: 709.881
• InChiKey: VCDWVMFXMSHMCZ-UGWDLRSTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  50
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  156
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  11-N-(4-azido-butyl)-6-O-methyl-5-O-desosaminyl-3-oxo-erythronolide A 11,12-carbamate 在 potassium tert-butylate 、 copper(II) sulfate 、 sodium ascorbate 作用下， 以 四氢呋喃 、 水 、 叔丁醇 为溶剂， 反应 17.08h， 生成 索利霉素
  参考文献：
  名称：

  [EN] 14-MEMBERED KETOLIDES AND METHODS OF THEIR PREPARATION AND USE
  [FR] KÉTOLIDES À 14 CHAÎNONS ET LEURS PROCÉDÉS DE PRÉPARATION ET D'UTILISATION

  摘要：

  本文提供了一种制备新的14元环酮类化合物的方法，通过将东半部分和西半部分偶联，然后进行大环化，以及可选的官能化。还提供了合成这些酮类化合物的中间体，包括东部和西部部分。还提供了使用这些酮类化合物治疗传染病和炎症性疾病的药物组合物和方法。

  公开号：

  WO2016057798A1
• 作为产物：
  描述：

  克拉霉素 在 盐酸 、 甲醇 、 N-氯代丁二酰亚胺 、 二甲基硫 、 sodium hexamethyldisilazane 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 75.0h， 生成 11-N-(4-azido-butyl)-6-O-methyl-5-O-desosaminyl-3-oxo-erythronolide A 11,12-carbamate
  参考文献：
  名称：

  Macrolide-Peptide Conjugates as Probes of the Path of Travel of the Nascent Peptides through the Ribosome

  摘要：

  Despite decades of research on the bacterial ribosome, the ribosomal exit tunnel is still poorly understood. Although it has been suggested that the exit tunnel is simply a convenient route of egress for the nascent chain, specific protein sequences serve to slow the rate of translation, suggesting some degree of interaction between the nascent peptide chain and the exit tunnel. To understand how the ribosome interacts with nascent peptide sequences, we synthesized and characterized a novel class of probe molecules. These peptidemacrolide (or peptolide) conjugates were designed to present unique peptide sequences to the exit tunnel. Biochemical and X-ray structural analyses of the interactions between these probes and the ribosome reveal interesting insights about the exit tunnel. Using translation inhibition and RNA structure probing assays, we find the exit tunnel has a relaxed preference for the directionality (N -> C or C -> N orientation) of the nascent peptides. Moreover, the X-ray crystal structure of one peptolide derived from a positively charged, reverse Nuclear Localization Sequence peptide, bound to the 70S bacterial ribosome, reveals that the macrolide ring of the peptolide binds in the same position as other macrolides. However, the peptide tail folds over the macrolide ring, oriented toward the peptidyl transferase center and interacting in a novel manner with 23S rRNA residue C2442 and His69 of ribosomal protein L4. These data suggest that these peptolides are viable probes for interrogating nascent peptideexit tunnel interaction.

  DOI：

  10.1021/cb5003224

文献信息

• Antibacterial agents
  申请人：MERCK SHARP & DOHME CORP.

  公开号：US09200026B2

  公开（公告）日：2015-12-01

  Described herein are novel macrolides, the preparation of novel macrolides, the use of novel macrolides for preventing, treating, or ameliorating various conditions, and the use of novel macrolides as antibacterial agents.

  本文描述了新型大环内酯类化合物，新型大环内酯类化合物的制备，新型大环内酯类化合物用于预防、治疗或改善各种疾病的用途，以及新型大环内酯类化合物作为抗菌剂的用途。
• An efficient entry to new sugar modified ketolide antibiotics
  作者：Alex Romero、Chang-Hsing Liang、Yu-Hung Chiu、Sulan Yao、Jonathan Duffield、Steven J. Sucheck、Ken Marby、David Rabuka、Po Yee Leung、Youe-Kong Shue、Yoshi Ichikawa、Chan-Kou Hwang

  DOI：10.1016/j.tetlet.2005.01.023

  日期：2005.2

  A new and efficient route to a ketolide aglycon served as a basis for the unprecedented 5-O-glyco-modification of ketolide antibiotics. Combined with an effective copper-catalyzed triazole-forming reaction a series of novel and potent ketolide antibiotics were synthesized.

  一种新的高效酮内酯糖苷配基途径，为酮内酯抗生素的5 - O-糖基修饰提供了基础。结合有效的铜催化三唑形成反应，合成了一系列新型有效的酮内酯抗生素。
• Synthesis and biological activity of new 5-O-sugar modified ketolide and 2-fluoro-ketolide antibiotics
  作者：Chang-Hsing Liang、Sulan Yao、Yu-Hung Chiu、Po Yee Leung、Nicole Robert、Jaime Seddon、Pam Sears、Chan-Kou Hwang、Yoshi Ichikawa、Alex Romero

  DOI：10.1016/j.bmcl.2005.01.027

  日期：2005.3

  A series of new triazole-containing ketolides and 2-fluoro-ketolides in which the 5-O-desosamine was replaced by unnatural sugars were synthesized and evaluated against relevant macrolide-sensitive and macrolide-resistant respiratory pathogens. Excellent in vitro antibacterial activities were demonstrated for ketolide analogues having the 6'-OBz-3'-dimethylamino-glucose and 6'-OBz-4'-deoxy-3'-dimethylamino-glucose substituents. (c) 2005 Elsevier Ltd. All rights reserved.