8-methylene-oleandomycin | 64774-87-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 8-methylene-oleandomycin
• 英文别名: deoxyoleandomycin；(3R,4S,5R,6S,7S,11R,12S,13R,14R)-6-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-12-hydroxy-4-[(2R,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-3,5,7,11,13,14-hexamethyl-9-methylidene-oxacyclotetradecane-2,10-dione
• CAS: 64774-87-4
• 化学式: C₃₅H₆₁NO₁₁
• 分子量: 671.869
• InChiKey: QWPJCGGEDCZKSJ-VXKHDWLYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  47
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  153
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  8-methylene-oleandomycin 在 镍 盐酸 、 sodium tetrahydroborate 、 四氧化钌 、 zinc(II) tetrahydroborate 、 碘代三甲硅烷 、 氢气 、 间氯过氧苯甲酸 、 magnesium bromide 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 乙醚 、 乙醇 、 乙酸乙酯 、 异丙醇 为溶剂， 反应 23.0h， 生成 (5R,8R,9R)-9-dihydro-8-methyl-epi-oleandolide
  参考文献：
  名称：

  由夹竹桃霉素衍生的聚酮内酯对映选择性合成大环内酯

  摘要：

  聚酮内酯，8-甲基-3,5,11-trioxo-oleandolide，它是从夹竹桃的新苷元通过四氧化钌氧化得到的，在溴化镁存在下被硼氢化锌立体选择性还原得到大环内酯，（ 5R,8R,9R)-9-dihydro-8-methyl-epi-oleandolide，收率良好。

  DOI：

  10.1246/cl.1987.187
• 作为产物：
  描述：

  竹桃霉素 在 chromium dichloride 作用下， 以 水 、 丙酮 为溶剂， 反应 0.75h， 生成 8-methylene-oleandomycin
  参考文献：
  名称：

  Deconstruction−Reconstruction Strategy for Accessing Valuable Polyketides. Preparation of the C15−C24 Stereopentad of Discodermolide

  摘要：

  An advanced, known intermediate for discodermolide synthesis was prepared by an efficient sequence from the readily available fermentation product oleandomycin. The scheme makes use of a new method for the direct cleavage of aminoglycosides, a critical double-bond isomerization, and a selective protection of two of three hydroxyl groups in a modified oleandolide. This synthesis illustrates a new strategy, "deconstruction-reconstruction", for accessing stereochemically complex polyketide building blocks.

  DOI：

  10.1021/ol702144u

文献信息

• New oleandomycin 9-oximes. Synthesis, characterization and biological activity.
  作者：GORJANA LAZAREVSKI、GABRIJELA KOBREHEL、SLOBODAN DOKIC、LIDIJA KOLACNY-BABIC、BISERKA KOJIC-PRODIC、DRAGAN JANKOVIC、VITOMIR PUNTAREC

  DOI：10.7164/antibiotics.47.349

  日期：——

  A series of the novel oleandomycin 9-oximes has been prepared and characterized by spectroscopic data and X-ray analysis. The antibacterial in vitro activities of the oximes (6-10) were compared with that of oleandomycin (1). Among the novel derivatives the most active compound was 8(R)-rriethyloleandomycin-9-oxime (9) in contrast to its 8(S)-isomer (10) which possessed only low potency. Some preliminary pharmacokinetic data of 9 confirmed its activity. Compound 9 has been advanced to further biological study.

  一系列新型奥利安霉素9-肟已被制备并通过光谱数据和X射线分析进行了表征。这些肟（6-10）的体外抗菌活性与奥利安霉素（1）进行了比较。在新衍生物中，活性最强的化合物是8(R)-三乙基奥利安霉素-9-肟（9），而其8(S)-异构体（10）则仅具有低活性。一些初步的药代动力学数据显示了9的活性。化合物9已被推进至进一步的生物研究。
• Impact of stereochemistry on the biological activity of novel oleandomycin derivatives
  作者：Jurica Bauer、Mark Vine、Ilija Čorić、Martina Bosnar、Ivanka Pašalić、Gordana Turkalj、Gorjana Lazarevski、Ognjen Čulić、Goran Kragol

  DOI：10.1016/j.bmc.2012.02.013

  日期：2012.4

  A set of 8-methylene-, 8-methyl-, and 8-methyl-9-dihydro-oleandomycin derivatives having different combinations of stereochemistries at positions C-8 and/or C-9 have been prepared in a chemoselective and stereoselective manner and tested in vitro for antibacterial activity and inhibition of IL-6 production. Configurations of the stereocenters at C-8 and C-9 were determined using 2D NMR techniques. We have shown that change of stereochemistry at these positions can exert a major influence on antibacterial activity as well as IL-6 inhibition, providing novel macrolide derivatives with diminished antibacterial and potent anti-inflammatory activity. In addition, the anti-inflammatory activity observed in vitro was confirmed in an in vivo model of lipopolysaccharide-induced inflammation. (C) 2012 Elsevier Ltd. All rights reserved.
• An Enantioselective Synthesis of a Macrolide from the Polyketide Lactone Derived from Oleandomycin
  作者：Kuniaki Tatsuta、Yoshiyuki Kobayashi、Kohji Akimoto、Mitsuhiro Kinoshita

  DOI：10.1246/cl.1987.187

  日期：1987.1.5

  The polyketide lactone, 8-methyl-3,5,11-trioxo-oleandolide, which is obtained from a new aglycone of oleandomycin by ruthenium tetraoxide oxidation, is stereoselectively reduced by zinc borohydride in the presence of magnesium bromide to give a macrolide, (5R,8R,9R)-9-dihydro-8-methyl-epi-oleandolide in a good yield.

  聚酮内酯，8-甲基-3,5,11-trioxo-oleandolide，它是从夹竹桃的新苷元通过四氧化钌氧化得到的，在溴化镁存在下被硼氢化锌立体选择性还原得到大环内酯，（ 5R,8R,9R)-9-dihydro-8-methyl-epi-oleandolide，收率良好。
• Deconstruction−Reconstruction Strategy for Accessing Valuable Polyketides. Preparation of the C15−C24 Stereopentad of Discodermolide
  作者：Kathlyn A. Parker、Peng Wang

  DOI：10.1021/ol702144u

  日期：2007.11.1

  An advanced, known intermediate for discodermolide synthesis was prepared by an efficient sequence from the readily available fermentation product oleandomycin. The scheme makes use of a new method for the direct cleavage of aminoglycosides, a critical double-bond isomerization, and a selective protection of two of three hydroxyl groups in a modified oleandolide. This synthesis illustrates a new strategy, "deconstruction-reconstruction", for accessing stereochemically complex polyketide building blocks.