1α,3β-bis-(tert-butyldimethylsilyloxy)-20(R)-(1-benzyl-3-hydroxy-3-methylpyrrolidin-2-on-5-yl)methyl-9,10-secopregna-5(Z),7(E),10(19)-triene | 851229-00-0

• 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: 1α,3β-bis-(tert-butyldimethylsilyloxy)-20(R)-(1-benzyl-3-hydroxy-3-methylpyrrolidin-2-on-5-yl)methyl-9,10-secopregna-5(Z),7(E),10(19)-triene
• 英文别名: 5-[(2R)-2-[(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]propyl]-1-benzyl-3-hydroxy-3-methylpyrrolidin-2-one
• CAS: 851229-00-0
• 化学式: C₄₆H₇₅NO₄Si₂
• 分子量: 762.277
• InChiKey: BJAIYMXIGGJUNQ-KBNQQFDASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.76
• 重原子数：
  53
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1α,3β-bis-(tert-butyldimethylsilyloxy)-20(R)-(1-benzyl-3-hydroxy-3-methylpyrrolidin-2-on-5-yl)methyl-9,10-secopregna-5(Z),7(E),10(19)-triene 在 氟化氢吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以15%的产率得到(23S,25S)-N-Benzyl-1alpha,25-dihydroxyvitamin D3-26,23-lactam-1P
  参考文献：
  名称：

  Practical Synthesis and Evaluation of the Biological Activities of 1α,25-dihydroxyvitamin D₃ Antagonists, 1α,25-dihydroxyvitamin D₃-26,23-lactams. Designed on the Basis of the Helix 12-Folding Inhibition Hypothesis

  摘要：

  A practical synthetic route to novel vitamin D antagonists of DLAM (1 alpha.,25-dihydroxyvitamin D-3-26,23lactam) was developed from vitamin D-2 via the 1,3-dipolar cycloaddition reaction as a key step. Six DLAM derivatives (24 compounds) with a variety of nitrogen substituents and stereochemistries at C23 and C25 were synthesized. Among these new derivatives, (23S,25S)-DLAM isomers bound effectively to VDRs and showed antagonistic activity in the HL-60 cell differentiation inhibition assay. The importance of the substituent on the nitrogen of DLAMs for antagonistic activity was also suggested by computational docking studies.

  DOI：

  10.1021/jm050738x
• 作为产物：
  描述：

  1α,3β-bis-(tert-butyldimethylsilyloxy)-20(R)-benzyliminomethyl-9,10-secopregna-5(Z),7(E),10(19)-triene N-oxide 在 sodium tetrahydroborate 、 hexacarbonyl molybdenum 作用下， 以 水 、 甲苯 、 乙腈 为溶剂， 反应 6.0h， 生成 1α,3β-bis-(tert-butyldimethylsilyloxy)-20(R)-(1-benzyl-3-hydroxy-3-methylpyrrolidin-2-on-5-yl)methyl-9,10-secopregna-5(Z),7(E),10(19)-triene
  参考文献：
  名称：

  Practical Synthesis and Evaluation of the Biological Activities of 1α,25-dihydroxyvitamin D₃ Antagonists, 1α,25-dihydroxyvitamin D₃-26,23-lactams. Designed on the Basis of the Helix 12-Folding Inhibition Hypothesis

  摘要：

  A practical synthetic route to novel vitamin D antagonists of DLAM (1 alpha.,25-dihydroxyvitamin D-3-26,23lactam) was developed from vitamin D-2 via the 1,3-dipolar cycloaddition reaction as a key step. Six DLAM derivatives (24 compounds) with a variety of nitrogen substituents and stereochemistries at C23 and C25 were synthesized. Among these new derivatives, (23S,25S)-DLAM isomers bound effectively to VDRs and showed antagonistic activity in the HL-60 cell differentiation inhibition assay. The importance of the substituent on the nitrogen of DLAMs for antagonistic activity was also suggested by computational docking studies.

  DOI：

  10.1021/jm050738x