(1S,2S,3R,4R,6R)-4-[(tert-butyldimethylsilyl)oxy]-1,3-dimethyl-7-oxabicyclo[4.1.0]heptan-2-ol | 1207735-01-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1S,2S,3R,4R,6R)-4-[(tert-butyldimethylsilyl)oxy]-1,3-dimethyl-7-oxabicyclo[4.1.0]heptan-2-ol
• 英文别名: (1S,2S,3R,4R,6R)-4-[tert-butyl(dimethyl)silyl]oxy-1,3-dimethyl-7-oxabicyclo[4.1.0]heptan-2-ol
• CAS: 1207735-01-0
• 化学式: C₁₄H₂₈O₃Si
• 分子量: 272.46
• InChiKey: MXJAMJMWBQORNF-ILOGHGLZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.94
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1S,2S,3R,4R,6R)-4-[(tert-butyldimethylsilyl)oxy]-1,3-dimethyl-7-oxabicyclo[4.1.0]heptan-2-ol 、 叔丁基二甲基氯硅烷 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以95%的产率得到(1S,2S,3R,4R,6R)-2,4-bis[(tert-butyldimethylsilyl)oxy]-1,3-dimethyl-7-oxabicyclo[4.1.0]heptane
  参考文献：
  名称：

  Structure−Function Relationships and Crystal Structures of the Vitamin D Receptor Bound 2α-Methyl-(20S,23S)- and 2α-Methyl-(20S,23R)-epoxymethano-1α,25-dihydroxyvitamin D₃

  摘要：

  The vitamin D nuclear receptor is a ligand-dependent transcription factor that controls multiple biological responses such as cell proliferation, immune responses, and bone mineralization. Numerous 1 alpha,25(OH)(2)D-3 analogues, which exhibit low calcemic side effects and/or antitumoral properties, have been synthesized. We recently showed that the synthetic analogue (20S,23S)-epoxymethano-1 alpha,25-dihydroxyvitamin D-3 (2a) acts as a 1 alpha,25(OH)(2)D-3 superagonist and exhibits both antiproliferative and prodifferentiating properties in vitro. Using this information and on the basis of the crystal structures of human VDR ligand binding domain (hVDR LBD) bound to 1 alpha,25(OH)(2)D-3,2 alpha-methyl-1 alpha,25(OH)(2)D-3, or 2a, we designed a novel analogue, 2 alpha-methyl-(20S,23S)-epoxymethano-1 alpha,25-dihydroxyvitamin D-3 (4a), in order to increase its transactivation potency. Here, we solved the crystal structures of the hVDR LBD in complex with the 4a (C23S) and its epimer 4b (C23R) and determined their correlation with specific biological outcomes.

  DOI：

  10.1021/jm9014636
• 作为产物：
  描述：

  (1R,3S,4R,6R)-4-[(tert-butyldimethylsilyl)oxy]-1,3-dimethyl-7-oxabicyclo[4.1.0]heptan-2-one 在 L-Selectride 、 双氧水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 12.0h， 以87%的产率得到(1S,2S,3R,4R,6R)-4-[(tert-butyldimethylsilyl)oxy]-1,3-dimethyl-7-oxabicyclo[4.1.0]heptan-2-ol
  参考文献：
  名称：

  Structure−Function Relationships and Crystal Structures of the Vitamin D Receptor Bound 2α-Methyl-(20S,23S)- and 2α-Methyl-(20S,23R)-epoxymethano-1α,25-dihydroxyvitamin D₃

  摘要：

  The vitamin D nuclear receptor is a ligand-dependent transcription factor that controls multiple biological responses such as cell proliferation, immune responses, and bone mineralization. Numerous 1 alpha,25(OH)(2)D-3 analogues, which exhibit low calcemic side effects and/or antitumoral properties, have been synthesized. We recently showed that the synthetic analogue (20S,23S)-epoxymethano-1 alpha,25-dihydroxyvitamin D-3 (2a) acts as a 1 alpha,25(OH)(2)D-3 superagonist and exhibits both antiproliferative and prodifferentiating properties in vitro. Using this information and on the basis of the crystal structures of human VDR ligand binding domain (hVDR LBD) bound to 1 alpha,25(OH)(2)D-3,2 alpha-methyl-1 alpha,25(OH)(2)D-3, or 2a, we designed a novel analogue, 2 alpha-methyl-(20S,23S)-epoxymethano-1 alpha,25-dihydroxyvitamin D-3 (4a), in order to increase its transactivation potency. Here, we solved the crystal structures of the hVDR LBD in complex with the 4a (C23S) and its epimer 4b (C23R) and determined their correlation with specific biological outcomes.

  DOI：

  10.1021/jm9014636