(20S)-1α,25-dihydroxy-2-methylene-26,27-dihomo-19-norvitamin D₃ | 364059-44-9

• 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: (20S)-1α,25-dihydroxy-2-methylene-26,27-dihomo-19-norvitamin D₃
• 英文别名: 19-nor-26,27-dimethyl-20(S)-2-methylene-1α,25-dihydroxyvitamin D3；(1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2S)-6-ethyl-6-hydroxyoctan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol
• CAS: 364059-44-9
• 化学式: C₂₉H₄₈O₃
• 分子量: 444.698
• InChiKey: PRSMNTCFGOCDOZ-USLQEWEHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (20S)-1α,25-dihydroxy-2-methylene-26,27-dihomo-19-norvitamin D₃ 在 Wilkinson's catalyst 氢气 作用下， 以 苯 为溶剂， 反应 5.5h， 生成 (20S)-1α,25-dihydroxy-2β-methyl-26,27-dihomo-19-norvitamin D₃ 、 (20S)-1α,25-dihydroxy-2α-methyl-26,27-dihomo-19-norvitamin D₃
  参考文献：
  名称：

  New highly calcemic 1α,25-dihydroxy-19-norvitamin D3 compounds with modified side chain: 26,27-dihomo- and 26,27-dimethylene analogs in 20S-series

  摘要：

  New highly potent 2-substituted (20S)-1alpha,25-dihydroxy-19-norvitamin D-3 analogs with elongated side chain were prepared by Wittig-Horner coupling of A-ring phosphine oxide with the corresponding protected (20S)-25-hydroxy Grundmann's ketones. Biologic evaluation in vitro and in vivo of the synthesized compounds was accomplished. All the synthesized vitamins possessing a 25-hydroxylated saturated side chain were slightly less active (3-5X) than 1alpha,25-dihydroxyvitamin D-3 in binding to the porcine intestinal vitamin D receptor and significantly more potent (12-150X) in causing differentiation of HL-60 cells. In vivo, 2-methylene-26,27-dihomo and 2alpha-methyl-26,27-dimethylene analogs were at least 10 times more active, and 2alpha-methyl-26,27-dihomo compound at least 5 times more active than the vitamin D hormone both in stimulating intestinal calcium transport and bone calcium mobilization (serum calcium increase). It was also established that a 260 pmol dose of the corresponding 2beta-methyl analogs had a similar effect on intestinal calcium transport and a much more pronounced effect on bone calcium mobilization as the same dose of 1alpha,25-dihydroxyvitamin D-3. (C) 2002 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(01)00156-8
• 作为产物：
  描述：

  (1R,3aR,7aR)-1-((S)-5-Ethyl-5-hydroxy-1-methyl-heptyl)-7a-methyl-octahydro-inden-4-one 在 2,6-二甲基吡啶 、 正丁基锂 、 AG 50W-X₄ resin 作用下， 以 四氢呋喃 、 甲醇 、 苯 为溶剂， 反应 35.5h， 生成 (20S)-1α,25-dihydroxy-2-methylene-26,27-dihomo-19-norvitamin D₃
  参考文献：
  名称：

  New highly calcemic 1α,25-dihydroxy-19-norvitamin D3 compounds with modified side chain: 26,27-dihomo- and 26,27-dimethylene analogs in 20S-series

  摘要：

  New highly potent 2-substituted (20S)-1alpha,25-dihydroxy-19-norvitamin D-3 analogs with elongated side chain were prepared by Wittig-Horner coupling of A-ring phosphine oxide with the corresponding protected (20S)-25-hydroxy Grundmann's ketones. Biologic evaluation in vitro and in vivo of the synthesized compounds was accomplished. All the synthesized vitamins possessing a 25-hydroxylated saturated side chain were slightly less active (3-5X) than 1alpha,25-dihydroxyvitamin D-3 in binding to the porcine intestinal vitamin D receptor and significantly more potent (12-150X) in causing differentiation of HL-60 cells. In vivo, 2-methylene-26,27-dihomo and 2alpha-methyl-26,27-dimethylene analogs were at least 10 times more active, and 2alpha-methyl-26,27-dihomo compound at least 5 times more active than the vitamin D hormone both in stimulating intestinal calcium transport and bone calcium mobilization (serum calcium increase). It was also established that a 260 pmol dose of the corresponding 2beta-methyl analogs had a similar effect on intestinal calcium transport and a much more pronounced effect on bone calcium mobilization as the same dose of 1alpha,25-dihydroxyvitamin D-3. (C) 2002 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(01)00156-8

文献信息

• Efficient Process for Preparing Steroids and Vitamin D Derivatives With the Unnatural Configuration at C20 (20 Alpha-Methyl) from Pregnenolone
  申请人：Bridges Alexander James

  公开号：US20080171728A1

  公开（公告）日：2008-07-17

  Disclosed herein are methods for preparing steroids and Vitamin D derivatives having the unnatural beta (usually S) configuration at C20, the methods comprising the use of compounds of the formula: wherein R is as defined herein. Also disclosed are steroids and Vitamin D derivatives made using the methods disclosed herein and pharmaceutical compositions comprising said steroids and Vitamin D derivatives.

  本文披露了一种制备具有不寻常的β（通常为S）构型的C20处的类固醇和维生素D衍生物的方法，该方法包括使用以下式的化合物：其中R如本文所定义。还披露了使用本文披露的方法制备的类固醇和维生素D衍生物，以及包含该类固醇和维生素D衍生物的药物组合物。
• [EN] EFFICIENT PROCESSES FOR PREPARING STEROIDS AND VITAMIN D DERIVATIVES WITH THE UNNATURAL CONFIGURATION AT C20 (20 ALPHA-METHYL) FROM PREGNENOLONE<br/>[FR] PROCÉDÉS EFFICACES POUR LA PRÉPARATION DE STÉROÏDES ET DE DÉRIVÉS DE VITAMINE D PRÉSENTANT UNE CONFIGURATION ANORMALE EN C20 (20 ALPHA-MÉTHYL) À PARTIR DE PREGNÉNOLONE
  申请人：QUATRX PHARMACEUTICALS COMPANY

  公开号：WO2008089093A2

  公开（公告）日：2008-07-24

  [EN] Disclosed herein are methods for preparing steroids and Vitamin D derivatives having the unnatural beta (usually S) configuration at C20, the methods comprising the use of compounds of the formula: wherein R is as defined herein. Also disclosed are steroids and Vitamin D derivatives made using the methods disclosed herein and pharmaceutical compositions comprising said steroids and Vitamin D derivatives.
  [FR] L'invention concerne des procédés de préparation de stéroïdes et de dérivés de vitamine D présentant la configuration anormale bêta (normalement S) en C20, ces procédés utilisant notamment des composés représentés par la formule ci-jointe, dans laquelle R est tel que défini dans la description. L'invention concerne également des stéroïdes et des dérivés de vitamine D fabriqués par ces procédés, ainsi que des compositions pharmaceutiques comprenant lesdits stéroïdes et dérivés de vitamine D.