(20R)-1α,25-dihydroxy-21-(3-hydroxy-3-trideuteromethyl-4,4,4-trideutero-butyl)-26,26,26,27,27,27-hexafluoro-23-yne-cholecalciferol | 1187454-39-2

• 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: (20R)-1α,25-dihydroxy-21-(3-hydroxy-3-trideuteromethyl-4,4,4-trideutero-butyl)-26,26,26,27,27,27-hexafluoro-23-yne-cholecalciferol
• 英文别名: (1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-7a-methyl-1-[(6R)-11,11,11-trideuterio-1,1,1-trifluoro-2,10-dihydroxy-10-(trideuteriomethyl)-2-(trifluoromethyl)undec-3-yn-6-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol
• CAS: 1187454-39-2
• 化学式: C₃₂H₄₄F₆O₄
• 分子量: 612.642
• InChiKey: VSOWXEHVBCDXAY-CVRMBSQLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  42
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  80.9
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (6R)-6-[(1R,3aS,4E,7aR)-4-[(2Z)-2-[(3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylidenecyclohexylidene]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]-11,11,11-trideuterio-1,1,1-trifluoro-10-(trideuteriomethyl)-2-(trifluoromethyl)-10-trimethylsilyloxyundec-3-yn-2-ol 、 [(1S,3Z,5R)-3-[(2E)-2-[(1R,3aS,7aR)-7a-methyl-1-[(6R)-11,11,11-trideuterio-1,1,1-trifluoro-10-(trideuteriomethyl)-2-(trifluoromethyl)-2,10-bis(trimethylsilyloxy)undec-3-yn-6-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-5-[tert-butyl(dimethyl)silyl]oxy-2-methylidenecyclohexyl]oxy-tert-butyl-dimethylsilane 在 四丁基氟化铵 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 45.0h， 以69.3%的产率得到(20R)-1α,25-dihydroxy-21-(3-hydroxy-3-trideuteromethyl-4,4,4-trideutero-butyl)-26,26,26,27,27,27-hexafluoro-23-yne-cholecalciferol
  参考文献：
  名称：

  Calcitriol Derivatives with Two Different Side Chains at C-20. V. Potent Inhibitors of Mammary Carcinogenesis and Inducers of Leukemia Differentiation

  摘要：

  Calcitriol is implicated in many cellular functions including cellular growth and differentiation, thus explaining its antitumor effects. It was shown that gemini, the calcitriol derivative containing two side chain at C20, is also active in gene transcription with enhanced antitumor activity. We have now further optimized both the A-ring and the two side chains. The chemical structures of the resulting 18 geminis were correlated with biological activities. Those containing the 1 alpha-fluoro A-ring are the least active. Those featuring 23-yne and 23(E) side-chains are generally more active in human breast cancer cell growth inhibition and human leukemia cell differentiation induction than their 23(Z) counterparts. On the basis of these evaluations, we selected as lead compound a 20(R) gemini, related to calcitriol in terms of it is A-ring, where one side chain was modified by introduction of a 23-yne function and replacement of the geminal methyl groups with trifluoromethyl groups, the other created by extension of C21 with a 3-hydroxy-3-trideuteromethyl-4,4,4-triduetero-butyl moiety.

  DOI：

  10.1021/jm900780q