1α,2α-epoxyandrostan-17-one | 1373116-42-7

• 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: 1α,2α-epoxyandrostan-17-one
• 英文别名: (1S,2S,3R,5S,8S,11R,12S,16S)-2,16-dimethyl-4-oxapentacyclo[9.7.0.02,8.03,5.012,16]octadecan-15-one
• CAS: 1373116-42-7
• 化学式: C₁₉H₂₈O₂
• 分子量: 288.43
• InChiKey: YXAUFXZLJCMJMC-NGUVMQQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  29.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  17-beta-羟基-5alpha-雄甾-1-烯-3-酮乙酸盐 在 Jones reagent 、 甲酸 、 氯化亚砜 、 双氧水 、 lithium tri-t-butoxyaluminum hydride 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 、 苯 为溶剂， 反应 21.05h， 生成 1α,2α-epoxyandrostan-17-one
  参考文献：
  名称：

  New Structure–Activity Relationships of A- and D-Ring Modified Steroidal Aromatase Inhibitors: Design, Synthesis, and Biochemical Evaluation

  摘要：

  A- and D-ring androstenedione derivatives were synthesized and tested for their abilities to inhibit aromatase. In one series, C-3 hydroxyl derivatives were studied leading to a very active compound, when the C-3 hydroxyl group assumes 3 beta stereochemistry (1, IC50 = 0.18 mu M). In a second series, the influence of double bonds or epoxide functions in different positions along the A-ring was studied. Among epoxides, the 3,4-epoxide 15 showed the best activity (IC50 = 0.145 mu M) revealing the possibility of the 3,4-oxiran oxygen resembling the C-3 carbonyl group of androstenedione. Among olefins, the 4,5-olefin 12 (IC50 = 0.135 mu M) revealed the best activity, pointing out the importance of planarity in the A,B-ring junction near C-5. C-4 acetoxy and acetylsalicyloxy derivatives were also studied showing that bulky substituents in C-4 diminish the activity. In addition, IFD simulations helped to explain the recognition of the C-3 hydroxyl derivatives (1 and 2) as well as 15 within the enzyme.

  DOI：

  10.1021/jm300262w

文献信息

• New Structure–Activity Relationships of A- and D-Ring Modified Steroidal Aromatase Inhibitors: Design, Synthesis, and Biochemical Evaluation
  作者：Carla Varela、Elisiário J. Tavares da Silva、Cristina Amaral、Georgina Correia da Silva、Teresa Baptista、Stefano Alcaro、Giosuè Costa、Rui A. Carvalho、Natércia A. A. Teixeira、Fernanda M. F. Roleira

  DOI：10.1021/jm300262w

  日期：2012.4.26

  A- and D-ring androstenedione derivatives were synthesized and tested for their abilities to inhibit aromatase. In one series, C-3 hydroxyl derivatives were studied leading to a very active compound, when the C-3 hydroxyl group assumes 3 beta stereochemistry (1, IC50 = 0.18 mu M). In a second series, the influence of double bonds or epoxide functions in different positions along the A-ring was studied. Among epoxides, the 3,4-epoxide 15 showed the best activity (IC50 = 0.145 mu M) revealing the possibility of the 3,4-oxiran oxygen resembling the C-3 carbonyl group of androstenedione. Among olefins, the 4,5-olefin 12 (IC50 = 0.135 mu M) revealed the best activity, pointing out the importance of planarity in the A,B-ring junction near C-5. C-4 acetoxy and acetylsalicyloxy derivatives were also studied showing that bulky substituents in C-4 diminish the activity. In addition, IFD simulations helped to explain the recognition of the C-3 hydroxyl derivatives (1 and 2) as well as 15 within the enzyme.