1α,3β-Bis<(methoxycarbonyl)oxy>-23,24-dinor-5,7-choladien-22-ol

• 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<(methoxycarbonyl)oxy>-23,24-dinor-5,7-choladien-22-ol
• 英文别名: 1α,3β-bis(methoxycarbonyloxy)-22-hydroxy-23,24-bisnorchola-5,7-diene；1α,3β-Bis[(methoxycarbonyl)oxy]-23,24-dinor-5,7-choladien-22-ol；[(1S,3R,9S,10R,13R,14R,17R)-17-[(2S)-1-hydroxypropan-2-yl]-1-methoxycarbonyloxy-10,13-dimethyl-2,3,4,9,11,12,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-yl] methyl carbonate
• 化学式: C₂₆H₃₈O₇
• 分子量: 462.584
• InChiKey: XVCGUBZUYDHRSV-IYOQTFQMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  91.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1α,3β-Bis<(methoxycarbonyl)oxy>-23,24-dinor-5,7-choladien-22-ol 在 4-二甲氨基吡啶 、 magnesium 、 potassium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 16.67h， 生成 阿法骨化醇
  参考文献：
  名称：

  Continuous-flow synthesis of activated vitamin D3 and its analogues

  摘要：

  实现了一种高效的两-stage连续流合成1α,25-(OH)2-维生素D3（活性维生素D3）及其类似物的方法。该方法使用高强度且经济的光源，即高压汞灯，获得了理想产品，且产率令人满意。此外，我们的方法不需要中间体的纯化或高稀释条件。

  DOI：

  10.1039/c2ob25511a

文献信息

• Stereoselective syntheses of (22R)- and (22S)-22-methyl-1.alpha.,25-dihydroxyvitamin D3: active vitamin D3 analogs with restricted side-chain conformation
  作者：Keiko Yamamoto、Jun Takahashi、Kazuhiko Hamano、Sachiko Yamada、Kentaro Yamaguchi、Hector F. DeLuca

  DOI：10.1021/jo00061a029

  日期：1993.4

  (22R)- and (22S)-22-methyl-1alpha,25-dihydroxyvitamin D3 (1b and 1c) were synthesized stereoselectively from 1alpha-hydroxylated C(22)-steroid 2. The two new vitamin D analogs, which have a side chain with restricted flexibility, were designed to allow the study of the stereochemical structure required to bind to the receptor of the active vitamin D3 (VDR). According to force-field calculations, the side chain of (22R)- and (22S)-methylated active vitamin D3 analogs (1b and 1c) adopts with more than 90% of the population gauche(+) and anti conformations, respectively, at the C(17-20-22-23) dihedral angle. Either the (22R)- or (22S)-methylated steroidal side chain was constructed with high stereoselectivity via a kinetically controlled conjugate addition of methylcopper reagent to (22E)- or (22Z)-22-en-24-ones (6 or 7), respectively, as a key step. The ability of the two analogs to bind to VDR was examined and only the (22S)-isomer (1c) showed significant activity. From the results, the side chain conformation best fitted to VDR was suggested to be the anti with respect to the C(17-20-22-23) dihedral angle.

  （22R)-和(22S)-22-甲基-1α,25-二羟基维生素D3（1b和1c）是从1α-羟基化的C(22)-甾体2立体选择性合成的。这两种新型维生素D类似物具有柔韧性较低的侧链，设计目的是为了研究与活性维生素D3受体(VDR)结合所需的立体化学结构。根据力场计算，（22R)-和(22S)-甲基化活性维生素D3类似物（1b和1c）的侧链在C(17-20-22-23)二面角下分别有超过90%的构象为gauche(+)和anti构型。通过动力学控制的甲基铜试剂对（22E)-或（22Z)-22-en-24-ones（6或7）的共轭加成，分别以高立体选择性构建了（22R)-或（22S)-甲基化甾体侧链，这是关键的步骤。这两种类似物与VDR的结合能力得到了检测，只有（22S)-异构体（1c）表现出显著的活性。根据实验结果，C(17-20-22-23)二面角下与VDR最佳匹配的侧链构象为anti构型。
• Selective capture of 1α,25-(OH) 2 -previtamin D 3 utilizing polymer-supported trialkylsilyl triflate in the synthesis of 1α,25-(OH) 2 -vitamin D 3
  作者：Takayuki Doi、Masahito Yoshida、Ichiro Hijikuro、Takashi Takahashi

  DOI：10.1016/j.tetlet.2004.05.125

  日期：2004.7

  Catch and release method utilizing polymer-support was investigated in the separation of 1alpha,25-(OH)(2) pre- and provitamin D-3. Polymer-supported alkyldiisopropylsityl triflate selectively captured the previtamin D-3 from a 26:74 mixture of pre- and provitamin D-3 produced by photoisomerization of provitamin D-3. (C) 2004 Elsevier Ltd. All rights reserved.
• Continuous-flow synthesis of activated vitamin D3 and its analogues
  作者：Shinichiro Fuse、Yuto Mifune、Nobutake Tanabe、Takashi Takahashi

  DOI：10.1039/c2ob25511a

  日期：——

  An efficient, two-stage, continuous-flow synthesis of 1α,25-(OH)2-vitamin D3 (activated vitamin D3) and its analogues was achieved. The developed method afforded the desired products in satisfactory yields using a high-intensity and economical light source, i.e., a high-pressure mercury lamp. In addition, our method required neither intermediate purification nor high-dilution conditions.

  实现了一种高效的两-stage连续流合成1α,25-(OH)2-维生素D3（活性维生素D3）及其类似物的方法。该方法使用高强度且经济的光源，即高压汞灯，获得了理想产品，且产率令人满意。此外，我们的方法不需要中间体的纯化或高稀释条件。