1α,3β-bis-(tert-butyldimethylsilyloxy)-20(R)-(2-benzyl-5-methoxycarbonyl-5-methylisoxazolidin-3-yl)methyl-9,10-secopregna-5(Z),7(E),10(19)-triene | 851228-83-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 1α,3β-bis-(tert-butyldimethylsilyloxy)-20(R)-(2-benzyl-5-methoxycarbonyl-5-methylisoxazolidin-3-yl)methyl-9,10-secopregna-5(Z),7(E),10(19)-triene
• 英文别名: methyl 3-[(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]-2-benzyl-5-methyl-1,2-oxazolidine-5-carboxylate
• CAS: 851228-83-6
• 化学式: C₄₇H₇₇NO₅Si₂
• 分子量: 792.303
• InChiKey: PYOAKGRYGRKQPX-FMPXYUCCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.35
• 重原子数：
  55
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1α,3β-bis-(tert-butyldimethylsilyloxy)-20(R)-(2-benzyl-5-methoxycarbonyl-5-methylisoxazolidin-3-yl)methyl-9,10-secopregna-5(Z),7(E),10(19)-triene 在 sodium tetrahydroborate 、 hexacarbonyl molybdenum 作用下， 以 水 、 乙腈 为溶剂， 反应 4.0h， 以55%的产率得到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
• 作为产物：
  描述：

  1α,3β-bis-(tert-butyldimethylsilyloxy)-9,10-secopregna-5(Z),7(E),10(19)-triene-20(R)-methyl p-toluenesulfonate 在 二异丁基氢化铝 、 三乙胺 作用下， 以 正己烷 、 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 8.0h， 生成 1α,3β-bis-(tert-butyldimethylsilyloxy)-20(R)-(2-benzyl-5-methoxycarbonyl-5-methylisoxazolidin-3-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