6-O-methyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A | 348125-79-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-O-methyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A
• 英文别名: C6-methoxy-9-deoxo-9a-aza-9a-homoerythromycin A；(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyl-tetrahydropyran-2-yl]oxy-2-ethyl-3,4-dihydroxy-13-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyl-tetrahydropyran-2-yl]oxy-10-methoxy-3,5,8,10,12,14-hexamethyl-1-oxa-6-azacyclopentadecan-15-one；(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-3,4-dihydroxy-13-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-10-methoxy-3,5,8,10,12,14-hexamethyl-1-oxa-6-azacyclopentadecan-15-one
• CAS: 348125-79-1
• 化学式: C₃₈H₇₂N₂O₁₂
• 分子量: 748.996
• InChiKey: CENLJTYJANLOJT-BICOPXKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  52
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  178
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  6-O-methyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A 在 盐酸 、 potassium carbonate 作用下， 以 氯仿 、 丙酮 为溶剂， 生成 Acetic acid (2S,3R,4S,6R)-4-dimethylamino-2-((2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-2-ethyl-3,4,13-trihydroxy-10-methoxy-3,5,6,8,10,12,14-heptamethyl-15-oxo-1-oxa-6-aza-cyclopentadec-11-yloxy)-6-methyl-tetrahydro-pyran-3-yl ester
  参考文献：
  名称：

  通过9（E）-6-O-甲基-红霉素肟的贝克曼重排，合成6-O-甲基-阿奇霉素及其酮化物类似物。

  摘要：

  6-O-甲基-阿奇霉素及其氮杂-酮内酯类似物的合成是通过对9（E）-6-O-甲基-红霉素肟1进行贝克曼重排而实现的。与C14酮类相反像HMR 3647一样，氮杂-酮内酯也没有活性，因此表明添加3酮官能团和从14到15元环的环扩展可能对抗菌活性有害。

  DOI：

  10.1016/s0960-894x(98)00402-8
• 作为产物：
  描述：

  克拉霉素 在 吡啶 、 sodium tetrahydroborate 、 羟胺 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 水 、 异丙醇 为溶剂， 反应 140.0h， 生成 6-O-methyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A
  参考文献：
  名称：

  大环内酯类抗寄生虫药的化学和生物学

  摘要：

  大环内酯类抗菌剂通过靶向顶质体核糖体来抑制寄生虫增殖。出于确定缺乏抗菌活性的抗寄生虫大环内酯类的长期目标，我们系统地分析了红霉素类似物之间的构效关系，并研究了所选化合物的作用机制。两种先导化合物，N-苄基阿奇霉素 ( 11 ) 和N-苯丙基阿奇霉素( 30))，被鉴定为具有比红霉素或阿奇霉素显着更高的抗寄生虫活性和更低的抗菌活性。基于与细菌核糖体结合的阿奇霉素共晶结构的分子模型表明，由于与核糖体 L22 蛋白的物种特异性相互作用，去甲基阿奇霉素 N-9 位的取代基可以提高选择性。与其他大环内酯类化合物一样，这些先导化合物表现出强烈的“延迟死亡表型”；然而，它们对弓形虫复制的早期影响更为明显。

  DOI：

  10.1021/jm101593u

文献信息

• Novel 9a-carbamoyl- and 9a-thiocarbamoyl-3-decladinosyl-6-hydroxy and 6-methoxy derivatives of 15-membered macrolides
  作者：Zorica Marušić Ištuk、Stjepan Mutak、Nedjeljko Kujundžić、Goran Kragol

  DOI：10.1016/j.bmc.2007.04.021

  日期：2007.7

  An efficient method for the synthesis of diverse 9a-carbamoyl- and 9a-thiocarbamoyl-3-decladinosyl-6-hydroxy and 3-decladinosyl-6-methoxy derivatives of 15-membered azalides has been developed. These derivatives bear various alkyl and aryl groups attached to macrolide scaffold through urea or thiourea moieties at 9a position. Chemical transformations of hydroxy group at position C-3 afforded range of ketolides, anhydrolides, herniketals, cyclic ethers, and acylides. It has been shown that 6-hydroxy and 6-methoxy derivatives undergo different chemical transformations under otherwise identical reaction conditions. Antimicrobial properties of prepared compounds were evaluated. (c) 2007 Elsevier Ltd. All rights reserved.
• Novel 9a,11-bridged azalides: One-pot synthesis of N′-substituted 2-imino-1,3-oxazolidines condensed to an azalide aglycone
  作者：Zorica Marušić Ištuk、Ana Čikoš、Dubravka Gembarovski、Gorjana Lazarevski、Ivica Đilović、Dubravka Matković-Čalogović、Goran Kragol

  DOI：10.1016/j.bmc.2010.10.061

  日期：2011.1

  An efficient one-pot method for the synthesis of novel 9a,11-bridged 15-membered 9a-aza-9-deoxo-9a-homoerythromycin A and its 6-O-methyl analogue has been developed. The novel bicyclic azalide scaffold is characterized by an N'-substituted-2-imino-1,3-oxazolidine moiety bound to a macrolactone ring between positions 9a and 11. Removal of the cladinose sugar from the starting compounds allows easy preparation of a small series of such bicyclic 3-keto and 3,6-hemiketal azalide derivatives. A mechanism for the formation of N'-substituted-2-imino-1,3-oxazolidines is discussed. Antibacterial properties of the prepared compounds were evaluated. (C) 2010 Elsevier Ltd. All rights reserved.
• Fajdetic, Andrea; Kobrehel, Gabrijela; Lazarevski, Gorjana, Croatica Chemica Acta, 2009, vol. 82, # 4, p. 715 - 723
  作者：Fajdetic, Andrea、Kobrehel, Gabrijela、Lazarevski, Gorjana、Marusic-Istuk, Zorica、Mutak, Stjepan

  DOI：——

  日期：——
• Chemistry and Biology of Macrolide Antiparasitic Agents
  作者：Younjoo Lee、Jun Yong Choi、Hong Fu、Colin Harvey、Sandeep Ravindran、William R. Roush、John C. Boothroyd、Chaitan Khosla

  DOI：10.1021/jm101593u

  日期：2011.4.28

  antibacterial agents inhibit parasite proliferation by targeting the apicoplast ribosome. Motivated by the long-term goal of identifying antiparasitic macrolides that lack antibacterial activity, we have systematically analyzed the structure−activity relationships among erythromycin analogues and have also investigated the mechanism of action of selected compounds. Two lead compounds, N-benzylazithromycin (11)

  大环内酯类抗菌剂通过靶向顶质体核糖体来抑制寄生虫增殖。出于确定缺乏抗菌活性的抗寄生虫大环内酯类的长期目标，我们系统地分析了红霉素类似物之间的构效关系，并研究了所选化合物的作用机制。两种先导化合物，N-苄基阿奇霉素 ( 11 ) 和N-苯丙基阿奇霉素( 30))，被鉴定为具有比红霉素或阿奇霉素显着更高的抗寄生虫活性和更低的抗菌活性。基于与细菌核糖体结合的阿奇霉素共晶结构的分子模型表明，由于与核糖体 L22 蛋白的物种特异性相互作用，去甲基阿奇霉素 N-9 位的取代基可以提高选择性。与其他大环内酯类化合物一样，这些先导化合物表现出强烈的“延迟死亡表型”；然而，它们对弓形虫复制的早期影响更为明显。
• Synthesis of 6-O-methyl-azithromycin and its ketolide analogue via Beckmann rearrangement of 9(E)-6-O-methyl-erythromycin oxime
  作者：A. Denis、C. Agouridas

  DOI：10.1016/s0960-894x(98)00402-8

  日期：1998.9

  The synthesis of 6-O-methyl-azithromycin and its aza-ketolide analogue have been achieved by carrying out the Beckmann rearrangement of the readily available 9(E)-6-O-methyl-erythromycin oxime 1. In contrast to the C14 ketolides like HMR 3647, the aza-ketolide turns out to be inactive, thus demonstrating that the addition of a 3 keto function and ring expansion, from 14 to 15 membered ring, could be

  6-O-甲基-阿奇霉素及其氮杂-酮内酯类似物的合成是通过对9（E）-6-O-甲基-红霉素肟1进行贝克曼重排而实现的。与C14酮类相反像HMR 3647一样，氮杂-酮内酯也没有活性，因此表明添加3酮官能团和从14到15元环的环扩展可能对抗菌活性有害。