(8R,9S)-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin | 133959-86-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (8R,9S)-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin
• 英文别名: EM900；(8R,9S)-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A；(1S,2S,3R,6R,7S,8S,9R,10R,12R)-3-[(2R,3R)-2,3-dihydroxypentan-2-yl]-9-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-7-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-2,6,8,10,12-pentamethyl-4,13-dioxabicyclo[8.2.1]tridecan-5-one
• CAS: 133959-86-1
• 化学式: C₃₇H₆₇NO₁₂
• 分子量: 717.938
• InChiKey: AKBSITQNMUKEMZ-ALENHZETSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  50
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  166
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  (8R,9S)-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin 在 吡啶 、 盐酸 、 甲醇 、 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 38.0h， 生成 EM918
  参考文献：
  名称：

  Novel 12-membered non-antibiotic macrolides from erythromycin A; EM900 series as novel leads for anti-inflammatory and/or immunomodulatory agents

  摘要：

  Herein, we report the design and synthesis of the novel 12-membered non-antibiotic macrolide (8R,9S)-8,9- dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM900), which was found to be a potent anti-inflammatory and/or immunomodulatory agent, capable of promoting monocyte to macrophage differentiation. This molecule shows improved acid stability, does not exhibit any anti-bacterial activity and has relatively low cytotoxicity against THP-1 cells. In addition, one of its analogues, (8R, 9S)-4 '',13-O-diacetyl- 8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM911), was found to be twice as effective as EM900. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.004
• 作为产物：
  描述：

  伪红霉素 A 烯醇醚 在 二氟乙酸 、 platinum(IV) oxide 、 氢气 作用下， 以 溶剂黄146 为溶剂， 20.0 ℃ 、506.66 kPa 条件下， 反应 4.0h， 以77%的产率得到(8R,9S)-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin
  参考文献：
  名称：

  Novel 12-membered non-antibiotic macrolides from erythromycin A; EM900 series as novel leads for anti-inflammatory and/or immunomodulatory agents

  摘要：

  Herein, we report the design and synthesis of the novel 12-membered non-antibiotic macrolide (8R,9S)-8,9- dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM900), which was found to be a potent anti-inflammatory and/or immunomodulatory agent, capable of promoting monocyte to macrophage differentiation. This molecule shows improved acid stability, does not exhibit any anti-bacterial activity and has relatively low cytotoxicity against THP-1 cells. In addition, one of its analogues, (8R, 9S)-4 '',13-O-diacetyl- 8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM911), was found to be twice as effective as EM900. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.004

文献信息

• Non-antibiotic 12-membered macrolides: design, synthesis and biological evaluation in a cigarette-smoking model
  作者：Akihiro Sugawara、Hideaki Shima、Akito Sueki、Tomoyasu Hirose、Hidehito Matsui、Hayato Nakano、Hideaki Hanaki、Kiyoko S Akagawa、Satoshi Ōmura、Toshiaki Sunazuka

  DOI：10.1038/ja.2015.91

  日期：2016.4

  anti-inflammatory and/or immunomodulatory effects, without possessing antibacterial activity. In this article, we report that the new macrolide derivative (8R,9S) -de(3'-N-methyl)-3'-N-(p-chlorobenzyl)-de(3-O-cladinosyl)-3-dehydro-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A 12,13-carbonate (EM939) exhibited stronger promotive activity for monocyte to macrophage differentiation than that of the

  14元大环内酯类红霉素A具有三种不同的生物学特性，包括抗菌活性，胃肠道运动刺激活性以及抗炎和/或免疫调节作用。尽管使用具有抗炎和/或免疫调节活性的14和15元大环内酯类药物进行低剂量长期治疗可有效治疗弥漫性全细支气管炎和慢性鼻窦炎，但仍可能出现细菌耐药性。为了解决这个问题，我们开发了12元非抗生素大环内酯（8R，9S）-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A（EM900），可促进单核细胞向巨噬细胞的分化，抗炎和/或免疫调节作用的标记，但不具有抗菌活性。在本文中，我们报告了新的大环内酯衍生物（8R，9S）-de（3' -N-甲基）-3'-N-（对氯苄基）-de（3-O-cladinosyl）-3-dehydro-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A 12，
• Novel 12-membered non-antibiotic macrolides from erythromycin A; EM900 series as novel leads for anti-inflammatory and/or immunomodulatory agents
  作者：Akihiro Sugawara、Akito Sueki、Tomoyasu Hirose、Kenichiro Nagai、Hiroaki Gouda、Shuichi Hirono、Hideaki Shima、Kiyoko S. Akagawa、Satoshi Ōmura、Toshiaki Sunazuka

  DOI：10.1016/j.bmcl.2011.04.004

  日期：2011.6

  Herein, we report the design and synthesis of the novel 12-membered non-antibiotic macrolide (8R,9S)-8,9- dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM900), which was found to be a potent anti-inflammatory and/or immunomodulatory agent, capable of promoting monocyte to macrophage differentiation. This molecule shows improved acid stability, does not exhibit any anti-bacterial activity and has relatively low cytotoxicity against THP-1 cells. In addition, one of its analogues, (8R, 9S)-4 '',13-O-diacetyl- 8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM911), was found to be twice as effective as EM900. (C) 2011 Elsevier Ltd. All rights reserved.