(E,2S,4R,5S,6R,9R,11R,16R)-18-[tert-butyl(dimethyl)silyl]oxy-9-hydroxy-4,11,12,16-tetramethyl-14-methylidene-5,6,11-tris(triethylsilyloxy)-2-trimethylsilyloxyoctadec-12-en-7-one | 1422463-08-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (E,2S,4R,5S,6R,9R,11R,16R)-18-[tert-butyl(dimethyl)silyl]oxy-9-hydroxy-4,11,12,16-tetramethyl-14-methylidene-5,6,11-tris(triethylsilyloxy)-2-trimethylsilyloxyoctadec-12-en-7-one
• CAS: 1422463-08-8
• 化学式: C₅₀H₁₀₆O₇Si₅
• 分子量: 959.815
• InChiKey: KDAKGWAOGRAYJT-AAMGOYSJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  15.46
• 重原子数：
  62
• 可旋转键数：
  35
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  83.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (3R,4S,5R,7R)-7-hydroxy-5-methyl-3,4-bis((triethylsilyl)oxy)octan-2-one 在 2,6-二甲基吡啶 、 甲醇 、 barium hydroxide octahydrate 、 三苯基膦 、 lithium diisopropyl amide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 5.83h， 生成 (E,2S,4R,5S,6R,9S,11R,16R)-18-[tert-butyl(dimethyl)silyl]oxy-9-hydroxy-4,11,12,16-tetramethyl-14-methylidene-5,6,11-tris(triethylsilyloxy)-2-trimethylsilyloxyoctadec-12-en-7-one 、 (E,2S,4R,5S,6R,9R,11R,16R)-18-[tert-butyl(dimethyl)silyl]oxy-9-hydroxy-4,11,12,16-tetramethyl-14-methylidene-5,6,11-tris(triethylsilyloxy)-2-trimethylsilyloxyoctadec-12-en-7-one
  参考文献：
  名称：

  Amphidinolide B: Total Synthesis, Structural Investigation, and Biological Evaluation

  摘要：

  The total syntheses of amphidinolide B-1 and the proposed structure of amphidinolide B-2 have been accomplished. Key aspects of this work include the development of a practical, non-transitionmetal-mediated method for the construction of the C-13-C-15 diene, the identification of alpha-chelation and dipole minimization models for diastereoselective methyl ketone aldol reactions, the discovery of a spontaneous Horner-Wadsworth-Emmons macrocyclization strategy, and the development of a novel late stage method for construction of an allylic epoxide moiety. The originally proposed structure for amphidinolide B-2 and diastereomers thereof display potent antitumor activities with IC50 values ranging from 3.3 to 94.5 nM against human solid and blood tumor cells. Of the different stereoisomers, the proposed structure of amphidinolide B-2 is over 12-fold more potent than the C-8,C-9-epimer and C-18-epimer in human DU145 prostate cancer cells. These data suggest that the epoxide stereochemistry is a significant factor for anticancer activity.

  DOI：

  10.1021/jo3026077

文献信息

• Amphidinolide B: Total Synthesis, Structural Investigation, and Biological Evaluation
  作者：Liang Lu、Wei Zhang、Sangkil Nam、David A. Horne、Richard Jove、Rich G. Carter

  DOI：10.1021/jo3026077

  日期：2013.3.15

  The total syntheses of amphidinolide B-1 and the proposed structure of amphidinolide B-2 have been accomplished. Key aspects of this work include the development of a practical, non-transitionmetal-mediated method for the construction of the C-13-C-15 diene, the identification of alpha-chelation and dipole minimization models for diastereoselective methyl ketone aldol reactions, the discovery of a spontaneous Horner-Wadsworth-Emmons macrocyclization strategy, and the development of a novel late stage method for construction of an allylic epoxide moiety. The originally proposed structure for amphidinolide B-2 and diastereomers thereof display potent antitumor activities with IC50 values ranging from 3.3 to 94.5 nM against human solid and blood tumor cells. Of the different stereoisomers, the proposed structure of amphidinolide B-2 is over 12-fold more potent than the C-8,C-9-epimer and C-18-epimer in human DU145 prostate cancer cells. These data suggest that the epoxide stereochemistry is a significant factor for anticancer activity.