(R)-6-{(1R,3aS,7aR)-4-[(R)-2-Methoxy-2-((1R,5R)-2-methylene-bicyclo[3.1.0]hex-1-yl)-eth-(E)-ylidene]-7a-methyl-octahydro-inden-1-yl}-2-methyl-heptan-2-ol | 74080-20-9

• 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: (R)-6-{(1R,3aS,7aR)-4-[(R)-2-Methoxy-2-((1R,5R)-2-methylene-bicyclo[3.1.0]hex-1-yl)-eth-(E)-ylidene]-7a-methyl-octahydro-inden-1-yl}-2-methyl-heptan-2-ol
• CAS: 74080-20-9
• 化学式: C₂₈H₄₆O₂
• 分子量: 414.672
• InChiKey: YCVJKHFELZVLTM-DXHFMDGASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.08
• 重原子数：
  30.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  29.46
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (R)-6-{(1R,3aS,7aR)-4-[(R)-2-Methoxy-2-((1R,5R)-2-methylene-bicyclo[3.1.0]hex-1-yl)-eth-(E)-ylidene]-7a-methyl-octahydro-inden-1-yl}-2-methyl-heptan-2-ol 在 吡啶 、 叔丁基过氧化氢 、 氢氧化钾 、 Wilkinson's catalyst 、 selenium(IV) oxide 、 氢气 作用下， 以 乙醇 、 二氯甲烷 、 苯 为溶剂， 反应 9.25h， 生成 (5Z,7E,1S,3R,10S)-9,10-seco-5,7-cholestadiene-1,3,25-triol
  参考文献：
  名称：

  Synthesis, Conformational Analysis, and Biological-Activity of the 1-α,25-Dihydroxy-10,19-Dihydrovitamin D3 Isomers

  摘要：

  The synthesis of the four 1 alpha,25-dihydroxy-10,19-dihydrovitamin D-3 stereoisomers (8-11) is described starting from 25-hydroxyvitamin D-3 (1c). Acetic acid-catalyzed cycloreversion of 1 alpha-hydroxylated 3,5-cyclovitamin D compound 14, produced by allylic oxidation of the intermediate cyclovitamin 13, afforded 1 alpha,25-dihydroxyvitamin D-3 3-acetate (16) and its 5E-isomer 17. Catalytic hydrogenation of 16 produced 10,18-dihydrovitamin acetates 20 and 21, whereas the same reaction of 17 resulted in the formation of SE-isomers 22 and 23. The analogous saturation of the 10,19-double bond in 14 gave 10(S), 19- and 10(R), 19-dihydrocyclovitamins 18 and 19 which after cycloreversion with acetic acid yielded different stereoisomeric pairs of 10,19-dihydrovitamin acetates 21, 23, 20, and 22, respectively. The stereochemistry and solution conformations of the A-ring of the 3-acetates 20-23 and their parent alcohols 8-11 were studied using H-1 NMR data. The A-ring chair population ratios of these stereoisomers were determined by the method of correlation of the observed coupling constants with the limiting values derived from cyclohexanol. The obtained results were confirmed by evaluation of interaction energies introduced by A-ring substituents and calculation of the free energy differences between the respective dihydrovitamin conformers. Conformational analyses of 10,19-dihydrovitamins were also carried out on model compounds 24-27 by using force-field calculations. Biological activity in vivo revealed that the 1 alpha,25-dihydroxy-10(S), 19-dihydrovitamin D-3 (9) followed by the 1 alpha,25-dihydroxy-10(S), 19-dihydro-(5E)-vitamin D-3 (11) to be the most active, while the 10(R)-isomers 8 and 10 possessed little or no activity. In vitro, the compounds possessing the most equatorial 1-hydroxyl, i.e., the 10(R)-isomers, were found most active, and the least equatorial were the least active. (C) 1994 Academic Press, Inc.

  DOI：

  10.1006/bioo.1994.1013
• 作为产物：
  描述：

  骨化二醇 在 吡啶 、 potassium hydrogencarbonate 作用下， 生成 (R)-6-{(1R,3aS,7aR)-4-[(R)-2-Methoxy-2-((1R,5R)-2-methylene-bicyclo[3.1.0]hex-1-yl)-eth-(E)-ylidene]-7a-methyl-octahydro-inden-1-yl}-2-methyl-heptan-2-ol
  参考文献：
  名称：

  Synthesis, Conformational Analysis, and Biological-Activity of the 1-α,25-Dihydroxy-10,19-Dihydrovitamin D3 Isomers

  摘要：

  The synthesis of the four 1 alpha,25-dihydroxy-10,19-dihydrovitamin D-3 stereoisomers (8-11) is described starting from 25-hydroxyvitamin D-3 (1c). Acetic acid-catalyzed cycloreversion of 1 alpha-hydroxylated 3,5-cyclovitamin D compound 14, produced by allylic oxidation of the intermediate cyclovitamin 13, afforded 1 alpha,25-dihydroxyvitamin D-3 3-acetate (16) and its 5E-isomer 17. Catalytic hydrogenation of 16 produced 10,18-dihydrovitamin acetates 20 and 21, whereas the same reaction of 17 resulted in the formation of SE-isomers 22 and 23. The analogous saturation of the 10,19-double bond in 14 gave 10(S), 19- and 10(R), 19-dihydrocyclovitamins 18 and 19 which after cycloreversion with acetic acid yielded different stereoisomeric pairs of 10,19-dihydrovitamin acetates 21, 23, 20, and 22, respectively. The stereochemistry and solution conformations of the A-ring of the 3-acetates 20-23 and their parent alcohols 8-11 were studied using H-1 NMR data. The A-ring chair population ratios of these stereoisomers were determined by the method of correlation of the observed coupling constants with the limiting values derived from cyclohexanol. The obtained results were confirmed by evaluation of interaction energies introduced by A-ring substituents and calculation of the free energy differences between the respective dihydrovitamin conformers. Conformational analyses of 10,19-dihydrovitamins were also carried out on model compounds 24-27 by using force-field calculations. Biological activity in vivo revealed that the 1 alpha,25-dihydroxy-10(S), 19-dihydrovitamin D-3 (9) followed by the 1 alpha,25-dihydroxy-10(S), 19-dihydro-(5E)-vitamin D-3 (11) to be the most active, while the 10(R)-isomers 8 and 10 possessed little or no activity. In vitro, the compounds possessing the most equatorial 1-hydroxyl, i.e., the 10(R)-isomers, were found most active, and the least equatorial were the least active. (C) 1994 Academic Press, Inc.

  DOI：

  10.1006/bioo.1994.1013

文献信息

• Novel synthesis of 1α,25-dihydroxy-19-norvitamin D from 25-hydroxyvitamin D
  作者：Asako Toyoda、Hazuki Nagai、Tomonari Yamada、Yusuke Moriguchi、Junko Abe、Toshio Tsuchida、Kazuo Nagasawa

  DOI：10.1016/j.tet.2009.09.115

  日期：2009.11

  19-Norvitamin D analogs 3a and 3b were synthesized from 25-hydroxyvitamin D, obtained via a bioconversion method. The synthetic route features a highly regio- and stereoselective hydroboration reaction to afford 25-hydroxy-3,5-cyclopropyl-vitamin D derivatives 12 having olefin at the C1–10-position.

  由通过生物转化方法获得的25-羟基维生素D合成19-Norvitamin D类似物3a和3b。合成路线的特征在于高度区域和立体选择性的硼氢化反应，以提供在C1-10位置具有烯烃的25-羟基-3,5-环丙基-维生素D衍生物12。
• Synthesis and Binding-analysis of 5E-[19-(2-bromoacetoxy)methyl]25-hydroxyvitamin D3 and 5E-25-hydroxyvitamin D3-19-methyl[(4-azido-2-nitro)phenyl]glycinate: Novel C19-modified Affinity and Photoaffinity Analogs of 25-hydroxyvitamin D3
  作者：James K Addo、Rahul Ray

  DOI：10.1016/s0039-128x(98)00009-9

  日期：1998.4

  Synthesis of novel C-19-modified affinity and photoaffinity analogs of vitamin D-3 and 25-hydroxyvitamin D-3(25-OH-D-3) is described A key step in the synthesis is a Horner-Emmons reaction between C-19-nor-cyclovitamin D-3-C-19-ketone or C-19-nor-25-hydroxy-cyclovitamin D-3-C-19-ketone and diethyl cyanomethylphosphonate. Competitive radioligand binding assays with human serum vitamin D-binding protein (DBP) and 5E-[19-(2-bromoacetoxy)methyl]25-hydroxyvitamin D-3 and 5E-25-hydroxyvitamin in D-3-19-methyl[4-azido-2-nitro)phenyl]glycinate, 25-OH-D-3-analogs containing affinity and photoaffinity probes at C-19-position, demonstrated that these compounds displaced radiolabeled 25-OH-D-3 from the binding pocket of DBP in it dose-dependent manner. Thus, these affinity and photoaffinity analogs are potentially useful in determining the ligand binding site topographies of DBP and possibly the vitamin D receptor. (C) 1998 by Elsevier Science Inc.