2α-methyl-20S,23R-epoxymethano-1α,25-dihydroxyvitamin D3 | 1207735-07-6

• 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: 2α-methyl-20S,23R-epoxymethano-1α,25-dihydroxyvitamin D3
• 英文别名: 2α-methyl-AMCR277B；(1s,2s,3r,5z,7e,14beta,17alpha,23r)-23-(2-Hydroxy-2-Methylpropyl)-2-Methyl-20,24-Epoxy-9,10-Secochola-5,7,10-Triene-1,3-Diol；(1R,2S,3S,5Z)-5-[(2E)-2-[(1S,3aS,7aS)-1-[(2S,4R)-4-(2-hydroxy-2-methylpropyl)-2-methyloxolan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methyl-4-methylidenecyclohexane-1,3-diol
• CAS: 1207735-07-6
• 化学式: C₂₉H₄₆O₄
• 分子量: 458.682
• InChiKey: CDTXSCLKUNDXBZ-MWPSFRNWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  69.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  [(1R,2S,3S,5Z)-5-[(2E)-2-[(1S,3aS,7aS)-7a-methyl-1-[(2S,4S)-2-methyl-4-(2-methyl-2-triethylsilyloxypropyl)oxolan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-3-[tert-butyl(dimethyl)silyl]oxy-2-methyl-4-methylidenecyclohexyl]oxy-tert-butyl-dimethylsilane 在 氟化氢吡啶 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 2.0h， 以0.036 g的产率得到2α-methyl-20S,23R-epoxymethano-1α,25-dihydroxyvitamin D3
  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