(5Z,7E)-(1S,2S,3R,20R)-9,10-seco-5,7,10(19)-cholestatriene-2-(4-hydroxybutyl)-1,3,25-triol

• 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: (5Z,7E)-(1S,2S,3R,20R)-9,10-seco-5,7,10(19)-cholestatriene-2-(4-hydroxybutyl)-1,3,25-triol
• 英文别名: 2α-(hydroxybutyl)-1α,25-dihydroxyvitamin D₃；(1R,2S,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-(4-hydroxybutyl)-4-methylidenecyclohexane-1,3-diol
• 化学式: C₃₁H₅₂O₄
• 分子量: 488.751
• InChiKey: BCDZYLNIANLXGJ-COENUSHESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  80.9
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (5S,6R)-6-(tert-butyldimethylsilanyloxy)-5-[(R)-1-(tert-butyldimethylsilanyloxy)allyl]non-8-ynnitrile 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 咪唑 、 sodium tetrahydroborate 、 二异丁基氢化铝 、 三苯基膦 作用下， 以 甲醇 、 二氯甲烷 、 三乙胺 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 19.5h， 生成 (5Z,7E)-(1S,2S,3R,20R)-9,10-seco-5,7,10(19)-cholestatriene-2-(4-hydroxybutyl)-1,3,25-triol
  参考文献：
  名称：

  Efficient and Versatile Synthesis of Novel 2α-Substituted 1α,25-Dihydroxyvitamin D₃ Analogues and Their Docking to Vitamin D Receptors

  摘要：

  Novel 2 alpha -substituted 1 alpha ,25-dihydroxyvitamin D-3 analogues with 2 alpha -alkyl and 2 alpha -hydroxyalkyl groups were systematically synthesized from D-xylose. Their conformation on binding to the ligand binding domain (LBD) of the vitamin D receptor was analyzed. It has been found that the 2 alpha -hydroxypropyl group best fits the cavity of the LBD, and the binding activity is three times higher than that for the natural hormone.

  DOI：

  10.1021/jo010375i

文献信息

• Stereocontrolled Total Synthesis of Calcitriol Derivatives: 1,25-Dihydroxy-2-(4'-hydroxybutyl)vitamin D3 Analogs of an Osteoporosis Drug
  作者：Gary H. Posner、Neil Johnson

  DOI：10.1021/jo00104a050

  日期：1994.12

  The diastereomeric 2 alpha- and 2 beta-(4'-hydroxybutyl) calcitriol analogs (-)-3 and (+)-3' were prepared in only 11 chemical operations, starting with 4 + 2-cycloaddition of commercially available methyl 2-pyrone-3-carboxylate. Highlights of this convergent and stereocontrolled synthetic approach are as follows: (1) retention of reactant dienophile geometry in the product bicyclic lactone, characteristic of a concerted inverse-electron-demand Diels-Alder cycloaddition; (2) an improved decarboxylation procedure involving chemospecific allyloxide opening of a lactone ring in the presence of a methyl ester and then non-high pressure palladium-promoted allylic ester decarboxylation; and (3) use of the enantiomercially pure C,D-ring chiron (+)-14 to resolve racemic A-ring phosphine oxide (+/-)-13. Relative binding affinities of the enantiomerically pure diastereomers (-)-3 and (+)-3' to the vitamin D binding protein and to the vitamin D receptor showed some unexpected trends. Diastereomer (+)-3' surprisingly bound more effectively to the vitamin D receptor than did the established osteoporosis drug ED-71 (1).
• Efficient and Versatile Synthesis of Novel 2α-Substituted 1α,25-Dihydroxyvitamin D₃ Analogues and Their Docking to Vitamin D Receptors
  作者：Yoshitomo Suhara、Ken-ichi Nihei、Masaaki Kurihara、Atsushi Kittaka、Kentaro Yamaguchi、Toshie Fujishima、Katsuhiro Konno、Naoki Miyata、Hiroaki Takayama

  DOI：10.1021/jo010375i

  日期：2001.12.1

  Novel 2 alpha -substituted 1 alpha ,25-dihydroxyvitamin D-3 analogues with 2 alpha -alkyl and 2 alpha -hydroxyalkyl groups were systematically synthesized from D-xylose. Their conformation on binding to the ligand binding domain (LBD) of the vitamin D receptor was analyzed. It has been found that the 2 alpha -hydroxypropyl group best fits the cavity of the LBD, and the binding activity is three times higher than that for the natural hormone.