3β-tert-butyldimethylsilyl-1α-tert-butyldimethylsilyloxy-25-trimethylsilyloxy-19-norvitamin D₃ | 599165-21-6

• 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: 3β-tert-butyldimethylsilyl-1α-tert-butyldimethylsilyloxy-25-trimethylsilyloxy-19-norvitamin D₃
• 英文别名: [(1S,3Z,5R)-3-[(2E)-2-[(1R,3aS,7aR)-7a-methyl-1-[(2R)-6-methyl-6-trimethylsilyloxyheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-5-[tert-butyl(dimethyl)silyl]oxy-2-methylidenecyclohexyl]oxy-tert-butyl-dimethylsilane
• CAS: 599165-21-6
• 化学式: C₄₂H₈₀O₃Si₃
• 分子量: 717.352
• InChiKey: CHTVPUCBCKQIST-LLNFYJGYSA-N

物化性质

• 沸点：
  635.5±55.0 °C(Predicted)
• 密度：
  0.93±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  13.62
• 重原子数：
  48
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3β-tert-butyldimethylsilyl-1α-tert-butyldimethylsilyloxy-25-trimethylsilyloxy-19-norvitamin D₃ 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 生成 骨化三醇
  参考文献：
  名称：

  Suzuki-Miyaura偶联有效聚合合成1alpha，25-dihydroxyvitamin D3及其类似物。

  摘要：

  [反应：请参见文本]通过A环中间体1的Suzuki-Miyaura偶联合成了1alpha，25-二羟基维生素D（3），该中间体是从容易获得的1,7-烯2与相应的硼酸酯化合物有效制备的C，D环部分。该方法适用于制备1α，25-二羟基维生素D（3）的des-C，D类似物。

  DOI：

  10.1021/ol0274007
• 作为产物：
  描述：

  艾地骨化醇中间体 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 3β-tert-butyldimethylsilyl-1α-tert-butyldimethylsilyloxy-25-trimethylsilyloxy-19-norvitamin D₃
  参考文献：
  名称：

  Stereoselective total synthesis of 1.alpha.,25-dihydroxycholecalciferol

  摘要：

  DOI：

  10.1021/ja00374a052

文献信息

• Process for the synthesis of vitamin d compounds and intermediates for the synthesis of the compounds
  申请人：Kashiwagi Hirotaka

  公开号：US20070135394A1

  公开（公告）日：2007-06-14

  An object of the present invention is to provide a process for synthesizing a vitamin D compound by simple procedures at lower costs. The present invention provides a process for preparing a vitamin D compound and an intermediate thereof, comprising the step of: (a) mixing a ketone or aldehyde, a Wittig reagent, and a base; or (b) mixing a ketone or aldehyde and a Wittig reagent, and then adding a base to the resulting mixture.

  本发明的一个目的是提供一种通过简单程序以更低成本合成维生素D化合物的方法。本发明提供了一种制备维生素D化合物及其中间体的方法，包括以下步骤：(a)混合酮或醛、威蒂格试剂和碱；或者(b)混合酮或醛和威蒂格试剂，然后向所得混合物中加入碱。
• Facile Construction of the 7,8‐Olefin Linkage in Vitamin D₃: A Practical Synthesis Benefiting the Vitamin D₃Analog Study
  作者：Yoshiyuki Ono、Hirotaka Kashiwagi、Tadakatsu Takahashi

  DOI：10.1080/00397910500503645

  日期：2006.5

  Abstract A facile procedure for construction of the 7,8‐olefin linkage in vitamin D3 is described. Treatment of a mixture of A‐ring phosphine oxide and CD‐ring ketone in THF with lithium hexamethyldisilazide (LHMDS) at −20°C followed by gradual heating to 50°C gives the key intermediate of vitamin D3 analogs in excellent yield. This simplified procedure makes possible small‐scale synthesis benefiting

  摘要描述了一种在维生素 D3 中构建 7,8-烯烃键的简便程序。在-20°C 下用六甲基二硅叠氮化锂 (LHMDS) 在 THF 中处理 A 环氧化膦和 CD 环酮的混合物，然后逐渐加热至 50°C，以优异的产率得到维生素 D3 类似物的关键中间体。这种简化的程序使小规模合成成为可能，有利于维生素 D3 类似物研究。
• New Convergent Synthesis of 1α,25-Dihydroxyvitamin D₃ and Its Analogues by Suzuki−Miyaura Coupling between A-Ring and C,D-Ring Parts
  作者：Takeshi Hanazawa、Akiko Koyama、Kunio Nakata、Sentaro Okamoto、Fumie Sato

  DOI：10.1021/jo0353435

  日期：2003.12.1

  A new convergent method for the synthesis of 1alpha,25-dihydroxyvitamin D-3 and its analogues has been developed that involves efficient preparation of the A-ring part la, (Z)-(3S,5R)-1-bromomethylene-3,5-bis(tert-butyldimethylsilyloxy)-2-methylenecyclohexane, starting from epichlorohydrin (4) and its Suzuki-Miyaura coupling reaction with the C,D-ring part 12. Thus, (R)-4 was converted to (3S,5R)-5-(tert-butyldimethylsilyloxy)-8-(trimethylsilyl)-oct-1-en-7-yn-3-ol (3a) through a ten-step reaction sequence in 49% overall yield. Compound 3a thus obtained was treated with a Ti(O-i-Pr)(4)/2 i-PrMgCl reagent and then with NBS to afford (Z)-(1S,2S,5R)-2-bromomethyl-3-[bromo(trimethylsilyl)methylene]-5-(tert-butyldimethylsilyloxy)cyclohexanol (10a) in 51% yield, from which la was obtained in 87% yield by sequential treatment with TBSCl/imidazole, DBU, and Cs2CO3. The resulting A-ring intermediate la was reacted with alkenylboronate 12 in the presence of a PdCl2(dppf) catalyst to furnish 1alpha,25-dihydroxyvitamin D-3 in 82% yield after protodesilylation. Similarly, all of the other three possible stereoisomers of A-ring parts 1b, 1c, and 1d were prepared, from which 1-epi-, 3-epi-, and 1,3-di-epi-1alpha,25-dihydroxyvitamin D-3 were synthesized by coupling with 12 in excellent yield, respectively. Starting from la and 1c, des-C,D-I(x,25-dihydroxyvitamin D-3 analogues, retiferol 13 and its 3-epi derivative, were also prepared, respectively.