3-((R)-2-{(1R,3aS,7aR)-4-[2-[(3S,5R)-3,5-Bis-(tert-butyl-dimethyl-silanyloxy)-2-methylene-cyclohex-(Z)-ylidene]-eth-(E)-ylidene]-7a-methyl-octahydro-inden-1-yl}-propyl)-5-methyl-2-(3-phenyl-propyl)-isoxazolidine-5-carboxylic acid methyl ester | 851228-87-0

• 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: 3-((R)-2-{(1R,3aS,7aR)-4-[2-[(3S,5R)-3,5-Bis-(tert-butyl-dimethyl-silanyloxy)-2-methylene-cyclohex-(Z)-ylidene]-eth-(E)-ylidene]-7a-methyl-octahydro-inden-1-yl}-propyl)-5-methyl-2-(3-phenyl-propyl)-isoxazolidine-5-carboxylic acid methyl ester
• 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]-5-methyl-2-(3-phenylpropyl)-1,2-oxazolidine-5-carboxylate
• CAS: 851228-87-0
• 化学式: C₄₉H₈₁NO₅Si₂
• 分子量: 820.357
• InChiKey: LNXNYIPHJNONSY-HDXBWJQVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.78
• 重原子数：
  57
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.73
• 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：

  3-((R)-2-{(1R,3aS,7aR)-4-[2-[(3S,5R)-3,5-Bis-(tert-butyl-dimethyl-silanyloxy)-2-methylene-cyclohex-(Z)-ylidene]-eth-(E)-ylidene]-7a-methyl-octahydro-inden-1-yl}-propyl)-5-methyl-2-(3-phenyl-propyl)-isoxazolidine-5-carboxylic acid methyl ester 在 sodium tetrahydroborate 、 hexacarbonyl molybdenum 、 氟化氢吡啶 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 9.0h， 生成 (23S,25R)-1alpha,25-dihydroxyvitamin D3-26,23-lactam-3P
  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：

  N-(3-phenylpropyl)hydroxylamine 在 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 4.0h， 生成 3-((R)-2-{(1R,3aS,7aR)-4-[2-[(3S,5R)-3,5-Bis-(tert-butyl-dimethyl-silanyloxy)-2-methylene-cyclohex-(Z)-ylidene]-eth-(E)-ylidene]-7a-methyl-octahydro-inden-1-yl}-propyl)-5-methyl-2-(3-phenyl-propyl)-isoxazolidine-5-carboxylic acid methyl ester
  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