26,26,26,27,27,27-Hexafluoro-1alpha,25-dihydroxy-23-oxo-vitamin D3 | 167893-03-0

• 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: 26,26,26,27,27,27-Hexafluoro-1alpha,25-dihydroxy-23-oxo-vitamin D3
• 英文别名: YB8IU8Woj4；(6R)-6-[(1R,3aS,4E,7aR)-4-[(2Z)-2-[(3S,5R)-3,5-dihydroxy-2-methylidenecyclohexylidene]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]-1,1,1-trifluoro-2-hydroxy-2-(trifluoromethyl)heptan-4-one
• CAS: 167893-03-0
• 化学式: C₂₇H₃₆F₆O₄
• 分子量: 538.571
• InChiKey: INOVHHVTWDEGJE-BPWFBYSLSA-N

物化性质

• 沸点：
  606.1±55.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  三甲基氯硅烷 、 N,O-双(三甲基硅烷基)三氟乙酰胺 、 26,26,26,27,27,27-Hexafluoro-1alpha,25-dihydroxy-23-oxo-vitamin D3 在 吡啶 作用下， 反应 1.0h， 生成 (R)-1,1,1-Trifluoro-6-{(1R,3aS,7aR)-7a-methyl-4-[2-[(3S,5R)-2-methylene-3,5-bis-trimethylsilanyloxy-cyclohex-(Z)-ylidene]-eth-(E)-ylidene]-octahydro-inden-1-yl}-2-trifluoromethyl-2-trimethylsilanyloxy-heptan-4-one 、 (1R,3aS,7aR)-7a-Methyl-4-[2-[(3S,5R)-2-methylene-3,5-bis-trimethylsilanyloxy-cyclohex-(Z)-ylidene]-eth-(E)-ylidene]-1-((Z)-(R)-6,6,6-trifluoro-1-methyl-5-trifluoromethyl-3,5-bis-trimethylsilanyloxy-hex-3-enyl)-octahydro-indene
  参考文献：
  名称：

  Metabolism of 26,26,26,27,27,27-F6-1α,25-dihydroxyvitamin D3 by CYP24: species-based difference between humans and rats

  摘要：

  The compound 26,26,26,27,27,27-F-6-1alpha,25(OH)(2)D-3 is a hexafluorinated analog of the active form of Vitamin D-3. The enhanced biological activity of F6-1alpha,25(OH)(2)D-3 is Considered to be related to a decreased metabolic inactivation of the compound in target tissues such as the kidneys, small intestine, and bones. Our previous study demonstrated that CYP24 is responsible for the metabolism of F-6-1alpha,25(OH)(2)D-3 inthetarget tissues. In this study, we compared the human and rat CYP24-dependent metabolism of F-6-1alpha,25(OH)(2)D-3 by using the Escherichia coli expression system. In the recombinant E. coli cells expressing human CYP24, bovine adrenodoxin and NADPH-adrenodoxin reductase, F-6-1alpha,25(OH)(2)D-3 was successively converted to F-6-1alpha,23S,25(OH)(3)D-3, F-6-23-oxo-1alpha,25(OH)(2)D-3, and the putative ether compound with the same molecular mass as F-6-1alpha,25(OH)(2)D-3. The putative ether was not observed in the recombinant E. coli cells expressing rat CYP24. These results indicate species-based difference between human and rat CYP24 in the metabolism of F-6-1alpha,25(OH)(2)D-3. In addition, the metabolite with a cleavage at the C-24-C-25 bond of F-6-1alpha,25(OH)(2)D-3 was detected as a minor metabolite in both human and rat CYP24. Although F6-1alpha,23S,25(OH)(3)D-3 and F-6-23-oxo-1alpha,25(OH)(2)D-3 had a high affinity for Vitamin D receptor, the side-chain cleaved metabolite and the putative ether showed extremely low affinity for Vitamin D receptor. These findings indicate that human CYP24 has a dual pathway for metabolic inactivation of F6-1alpha,25(OH)(2)D-3 while rat CYP24 has only one pathway. Judging from the fact that metabolism of F6-1alpha,25(OH)(2)D-3 in rat CYP24-harboring E. coli cells is quite similar to that in the target tissues of rat, the metabolism seen in human CYP24-harboring E. coli cells appear to exhibit the same metabolism as in human target tissues. Thus, this recombinant system harboring human CYP24 appears quite useful for predicting the metabolism and efficacy of Vitamin D analogs in human target tissues before clinical trials. (C) 2003 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0006-2952(03)00190-4
• 作为产物：
  描述：

  (R)-4-{(1R,3aS,7aR)-4-[2-[(S)-5-(tert-Butyl-dimethyl-silanyloxy)-2-methylene-cyclohex-(E)-ylidene]-eth-(E)-ylidene]-7a-methyl-octahydro-inden-1-yl}-pentan-2-ol 在 咪唑 、 selenium(IV) oxide 、 N-甲基吲哚酮 、 四丙基高钌酸铵 、 蒽 、 对甲苯磺酸 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 8.75h， 生成 26,26,26,27,27,27-Hexafluoro-1alpha,25-dihydroxy-23-oxo-vitamin D3
  参考文献：
  名称：

  Synthesis and biological evaluations of C-23-modified 26,26,26,27,27,27-F 6 -vitamin D 3 analogues

  摘要：

  A convenient synthetic method which could allow flexible modification at C-23 of 26,26,26,27,27,27-hexafluoro-1 alpha,25-dihydroxyvitamin D-3 (3) has been developed. An effective construction of hexafluoroacetone (HFA) aldol part on the side chain of 10 was achieved by aldol reaction with HFA gas. This route is also attractive as an approach to diverse 26,27-modified vitamin D3 analogues. The preliminary biological activities of 23-modifed 26,27-F-6 vitamin D3 analogues are evaluated. The potency of VDR affinities of the C-23-substituted analogues (keto group (4); OH group (5a,5b); fluorine atom (6a,6b); and oxetane ring (7a,7b)) was found to vary depending upon both the nature and stereochemistry of the substituents. In contrast, the HL-60 cell differentiation property was less varied than VDR affinity, and depended upon the nature rather than the stereochemistry of the substituents. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00106-1