(5E,7E,1S,3R,10R)-3-acetoxy-9,10-seco-5,7-cholestadiene-1,25-diol | 157637-98-4

• 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: (5E,7E,1S,3R,10R)-3-acetoxy-9,10-seco-5,7-cholestadiene-1,25-diol
• CAS: 157637-98-4
• 化学式: C₂₉H₄₈O₄
• 分子量: 460.698
• InChiKey: WCODSZIYCZHZMX-ZFWFONRBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.36
• 重原子数：
  33.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  66.76
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (5E,7E,1S,3R,10R)-3-acetoxy-9,10-seco-5,7-cholestadiene-1,25-diol 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以68%的产率得到1,25-二羟基二氢速甾醇 (3)
  参考文献：
  名称：

  Synthesis, Conformational Analysis, and Biological-Activity of the 1-α,25-Dihydroxy-10,19-Dihydrovitamin D3 Isomers

  摘要：

  The synthesis of the four 1 alpha,25-dihydroxy-10,19-dihydrovitamin D-3 stereoisomers (8-11) is described starting from 25-hydroxyvitamin D-3 (1c). Acetic acid-catalyzed cycloreversion of 1 alpha-hydroxylated 3,5-cyclovitamin D compound 14, produced by allylic oxidation of the intermediate cyclovitamin 13, afforded 1 alpha,25-dihydroxyvitamin D-3 3-acetate (16) and its 5E-isomer 17. Catalytic hydrogenation of 16 produced 10,18-dihydrovitamin acetates 20 and 21, whereas the same reaction of 17 resulted in the formation of SE-isomers 22 and 23. The analogous saturation of the 10,19-double bond in 14 gave 10(S), 19- and 10(R), 19-dihydrocyclovitamins 18 and 19 which after cycloreversion with acetic acid yielded different stereoisomeric pairs of 10,19-dihydrovitamin acetates 21, 23, 20, and 22, respectively. The stereochemistry and solution conformations of the A-ring of the 3-acetates 20-23 and their parent alcohols 8-11 were studied using H-1 NMR data. The A-ring chair population ratios of these stereoisomers were determined by the method of correlation of the observed coupling constants with the limiting values derived from cyclohexanol. The obtained results were confirmed by evaluation of interaction energies introduced by A-ring substituents and calculation of the free energy differences between the respective dihydrovitamin conformers. Conformational analyses of 10,19-dihydrovitamins were also carried out on model compounds 24-27 by using force-field calculations. Biological activity in vivo revealed that the 1 alpha,25-dihydroxy-10(S), 19-dihydrovitamin D-3 (9) followed by the 1 alpha,25-dihydroxy-10(S), 19-dihydro-(5E)-vitamin D-3 (11) to be the most active, while the 10(R)-isomers 8 and 10 possessed little or no activity. In vitro, the compounds possessing the most equatorial 1-hydroxyl, i.e., the 10(R)-isomers, were found most active, and the least equatorial were the least active. (C) 1994 Academic Press, Inc.

  DOI：

  10.1006/bioo.1994.1013
• 作为产物：
  描述：

  (7E)-(1S,3R,5R,6R)-6-methoxy-3,5-cyclo-9,10-seco-7,10(19)-cholestadiene-1,25-diol 在 Wilkinson's catalyst 、 氢气 作用下， 以 苯 为溶剂， 反应 8.25h， 生成 (5E,7E,1S,3R,10R)-3-acetoxy-9,10-seco-5,7-cholestadiene-1,25-diol
  参考文献：
  名称：

  Synthesis, Conformational Analysis, and Biological-Activity of the 1-α,25-Dihydroxy-10,19-Dihydrovitamin D3 Isomers

  摘要：

  The synthesis of the four 1 alpha,25-dihydroxy-10,19-dihydrovitamin D-3 stereoisomers (8-11) is described starting from 25-hydroxyvitamin D-3 (1c). Acetic acid-catalyzed cycloreversion of 1 alpha-hydroxylated 3,5-cyclovitamin D compound 14, produced by allylic oxidation of the intermediate cyclovitamin 13, afforded 1 alpha,25-dihydroxyvitamin D-3 3-acetate (16) and its 5E-isomer 17. Catalytic hydrogenation of 16 produced 10,18-dihydrovitamin acetates 20 and 21, whereas the same reaction of 17 resulted in the formation of SE-isomers 22 and 23. The analogous saturation of the 10,19-double bond in 14 gave 10(S), 19- and 10(R), 19-dihydrocyclovitamins 18 and 19 which after cycloreversion with acetic acid yielded different stereoisomeric pairs of 10,19-dihydrovitamin acetates 21, 23, 20, and 22, respectively. The stereochemistry and solution conformations of the A-ring of the 3-acetates 20-23 and their parent alcohols 8-11 were studied using H-1 NMR data. The A-ring chair population ratios of these stereoisomers were determined by the method of correlation of the observed coupling constants with the limiting values derived from cyclohexanol. The obtained results were confirmed by evaluation of interaction energies introduced by A-ring substituents and calculation of the free energy differences between the respective dihydrovitamin conformers. Conformational analyses of 10,19-dihydrovitamins were also carried out on model compounds 24-27 by using force-field calculations. Biological activity in vivo revealed that the 1 alpha,25-dihydroxy-10(S), 19-dihydrovitamin D-3 (9) followed by the 1 alpha,25-dihydroxy-10(S), 19-dihydro-(5E)-vitamin D-3 (11) to be the most active, while the 10(R)-isomers 8 and 10 possessed little or no activity. In vitro, the compounds possessing the most equatorial 1-hydroxyl, i.e., the 10(R)-isomers, were found most active, and the least equatorial were the least active. (C) 1994 Academic Press, Inc.

  DOI：

  10.1006/bioo.1994.1013