(3E,9E,12S,15E,17R,19S,22R,23S,24R,26S)-3,12,16,17,24,26-hexamethyl-14-methylidene-17,19,22,23-tetrakis(triethylsilyloxy)-1-oxacyclohexacosa-3,9,15-triene-2,8,21-trione | 1033588-14-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: (3E,9E,12S,15E,17R,19S,22R,23S,24R,26S)-3,12,16,17,24,26-hexamethyl-14-methylidene-17,19,22,23-tetrakis(triethylsilyloxy)-1-oxacyclohexacosa-3,9,15-triene-2,8,21-trione
• CAS: 1033588-14-5
• 化学式: C₅₆H₁₀₆O₈Si₄
• 分子量: 1019.79
• InChiKey: YWALLSZQXDSWHQ-BHQSLYOQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  16.42
• 重原子数：
  68
• 可旋转键数：
  20
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  97.4
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (3E,9E,12S,15E,17R,19S,22R,23S,24R,26S)-3,12,16,17,24,26-hexamethyl-14-methylidene-17,19,22,23-tetrakis(triethylsilyloxy)-1-oxacyclohexacosa-3,9,15-triene-2,8,21-trione 在 titanium(IV) isopropylate 、 叔丁基过氧化氢 、 dimethyl sulfide borane 、 (S)-2-甲基-CBS-恶唑硼烷 作用下， 以 四氢呋喃 、 癸烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 5.75h， 生成 (1R,2R,6E,10S,12R,13S,14R,17S,19R,20E,24R,26R)-2-hydroxy-7,10,12,19,20,24-hexamethyl-22-methylidene-13,14,17,19-tetrakis(triethylsilyloxy)-9,27-dioxabicyclo[24.1.0]heptacosa-6,20-diene-8,15-dione
  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
• 作为产物：
  描述：

  5-氧代戊酸甲酯 在 甲醇 、 正丁基锂 、 四丙基高钌酸铵 、 barium hydroxide octahydrate 、 2,4,6-三氯苯甲酰氯 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 38.91h， 生成 (3E,9E,12S,15E,17R,19S,22R,23S,24R,26S)-3,12,16,17,24,26-hexamethyl-14-methylidene-17,19,22,23-tetrakis(triethylsilyloxy)-1-oxacyclohexacosa-3,9,15-triene-2,8,21-trione
  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

• Total Synthesis of Cytotoxic Macrolide Amphidinolide B₁ and the Proposed Structure of Amphidinolide B₂
  作者：Liang Lu、Wei Zhang、Rich G. Carter

  DOI：10.1021/ja803012n

  日期：2008.6.1

  The first enantioselective total syntheses of cytotoxic macrolide amphidinolide B, and the proposed structure for amphidinolide B-2 have been accomplished. Key features of the syntheses include a diastereoselective aldol condensation, a spontaneous Wadsworth-Emmons `macrocyclization and a directed epoxidation/elimination sequence.
• 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.