1α,25-dihydroxy-21-(3-hydroxy-3-trideuteriomethyl-4,4,4-trideuteriobut-1-yl)-26,27-hexadeuterio-19-nor-cholecalciferol | 1432905-65-1

• 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: 1α,25-dihydroxy-21-(3-hydroxy-3-trideuteriomethyl-4,4,4-trideuteriobut-1-yl)-26,27-hexadeuterio-19-nor-cholecalciferol
• 英文别名: (1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[1,1,1,11,11,11-hexadeuterio-2,10-dihydroxy-2,10-bis(trideuteriomethyl)undecan-6-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]cyclohexane-1,3-diol
• CAS: 1432905-65-1
• 化学式: C₃₁H₅₄O₄
• 分子量: 502.672
• InChiKey: LKQDWHZSESKMAZ-SFEAAQOHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  80.9
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (1R,3aR,7aR)-7a-methyl-1-[6,6,6-trideuterio-5-(trideuteriomethyl)-1-[5,5,5-trideuterio-4-(trideuteriomethyl)-4-trimethylsilyloxy-pentyl]-5-trimethylsilyloxyhexyl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-one 在 正丁基锂 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 0.25h， 生成 1α,25-dihydroxy-21-(3-hydroxy-3-trideuteriomethyl-4,4,4-trideuteriobut-1-yl)-26,27-hexadeuterio-19-nor-cholecalciferol
  参考文献：
  名称：

  Diastereotopic and Deuterium Effects in Gemini

  摘要：

  Changing the geminal methyl groups on 1α,25-dihydroxyvitamin D3 and its analogues to the deuterio versions generally improves the bioactivity. Derivatives of 1α,25-dihydroxyvitamin D3 with two chains emanating at C20, commonly referred to as gemini, are subject to the same phenomenon. Additionally, gemini with different side chains are susceptible to bioactivity differentials where the C17-C20 threo configuration usually imparts higher activity than the corresponding erythro arrangement. In an effort to analyze the deuterium effect on gemini with minimal diastereotopic distortion, we synthesized gemini with equal side chains but introduced deuterium diastereospecifically on either chain. We solved the crystal structures of these compounds in the zebra fish zVDR ligand binding domain as complexes with NCoA-2 coactivator peptide and correlated the findings with growth inhibition in a breast cancer cell line.

  DOI：

  10.1021/jm400032t

文献信息

• Diastereotopic and Deuterium Effects in Gemini
  作者：Hubert Maehr、Natacha Rochel、Hong Jin Lee、Nanjoo Suh、Milan R. Uskokovic

  DOI：10.1021/jm400032t

  日期：2013.5.23

  Changing the geminal methyl groups on 1α,25-dihydroxyvitamin D3 and its analogues to the deuterio versions generally improves the bioactivity. Derivatives of 1α,25-dihydroxyvitamin D3 with two chains emanating at C20, commonly referred to as gemini, are subject to the same phenomenon. Additionally, gemini with different side chains are susceptible to bioactivity differentials where the C17-C20 threo configuration usually imparts higher activity than the corresponding erythro arrangement. In an effort to analyze the deuterium effect on gemini with minimal diastereotopic distortion, we synthesized gemini with equal side chains but introduced deuterium diastereospecifically on either chain. We solved the crystal structures of these compounds in the zebra fish zVDR ligand binding domain as complexes with NCoA-2 coactivator peptide and correlated the findings with growth inhibition in a breast cancer cell line.