(1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-acetoxy-2-((S)-2-(dimethylamino)-2,3-dimethylbutoxy)-1,6a,8,10a-tetramethyl-8-((R)-3-methylbutan-2-yl)-6-oxo-2,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-1H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid | 956102-41-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-acetoxy-2-((S)-2-(dimethylamino)-2,3-dimethylbutoxy)-1,6a,8,10a-tetramethyl-8-((R)-3-methylbutan-2-yl)-6-oxo-2,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-1H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid
• 英文别名: (1R,5S,6R,7R,10R,11R,14R,15S,20R,21R)-20-acetyloxy-21-[(2S)-2-(dimethylamino)-2,3-dimethylbutoxy]-5,7,10,15-tetramethyl-7-[(2R)-3-methylbutan-2-yl]-4-oxo-17-oxapentacyclo[13.3.3.01,14.02,11.05,10]henicos-2-ene-6-carboxylic acid
• CAS: 956102-41-3
• 化学式: C₄₀H₆₅NO₇
• 分子量: 671.959
• InChiKey: ZUVXSBIFQHTVNZ-KMFAUROCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  48
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (1R,5S,6R,7R,10R,11R,14R,15S,20R,21R)-20-acetyloxy-5,7,10,15-tetramethyl-7-[(2R)-3-methylbutan-2-yl]-21-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-17-oxapentacyclo[13.3.3.01,14.02,11.05,10]henicos-2-ene-6-carboxylic acid 在 甲酸 、 亚硝酸特丁酯 、 硫酸 、 palladium 10% on activated carbon 、 20 % Pd(OH)2/C 、 20 wt.% Pd(OH)2 on activated carbon 、 氨 、 氢气 、 potassium 2-methylbutan-2-olate 、 sodium cyanoborohydride 、 potassium carbonate 、 对甲苯磺酸 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 醋酸异丙酯 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， -10.0~78.0 ℃ 、1.31 MPa 条件下， 反应 107.0h， 生成 (1S,2R,3R,4aR,6aS,7R,8R,10aR,10bR,12aR)-3-acetoxy-2-((S)-2-(dimethylamino)-2,3-dimethylbutoxy)-1,6a,8,10a-tetramethyl-8-((R)-3-methylbutan-2-yl)-6-oxo-2,3,4,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-1H-1,4a-(methanooxymethano)chrysene-7-carboxylic acid
  参考文献：
  名称：

  Synthesis of Antifungal Glucan Synthase Inhibitors from Enfumafungin

  摘要：

  An efficient, new, and scalable semisynthesis of glucan synthase inhibitors 1 and 2 from the fermentation product enfumafungin 3 is described. The highlights of the synthesis include a high-yielding ether bond-forming reaction between a bulky sulfamidate 17 and alcohol 4 and a remarkably chemoselective, improved palladium(II)-mediated Corey-Yu allylic oxidation at the highly congested C-12 position of the enfumafungin core. Multi-hundred gram quantities of the target drug candidates 1 and 2 were prepared, in 12 linear steps with 25% isolated yield and 13 linear steps with 22% isolated yield, respectively.

  DOI：

  10.1021/jo300046v

文献信息

• Antifungal agents
  申请人：Balkovec M. James

  公开号：US20080009504A1

  公开（公告）日：2008-01-10

  The present invention relates to novel enfumafungin derivatives of formula I and pharmaceutically acceptable salts thereof, their synthesis, and their use as inhibitors of (1,3)-β-D-glucan synthase. The present compounds and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions comprising the present compounds and pharmaceutically acceptable salts thereof, are useful for treating or preventing antifungal infections and associated diseases and conditions.

  本发明涉及公式I的新型恩福马霉素衍生物及其药学上可接受的盐，它们的合成以及它们作为(1,3)-β-D-葡聚糖合酶抑制剂的用途。本化合物及其药学上可接受的盐，以及包括本化合物及其药学上可接受的盐的制药组合物，有用于治疗或预防抗真菌感染及相关疾病和病况的作用。
• US7863465B2
  申请人：——

  公开号：US7863465B2

  公开（公告）日：2011-01-04