(20R)-de-A,B-25-hydroxy-22-oxacholestan-8-one | 681434-00-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (20R)-de-A,B-25-hydroxy-22-oxacholestan-8-one
• CAS: 681434-00-4
• 化学式: C₁₇H₃₀O₃
• 分子量: 282.423
• InChiKey: RNNQSWKJXYHFRW-VWPFQQQWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.34
• 重原子数：
  20.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  46.53
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (20R)-de-A,B-25-hydroxy-22-oxacholestan-8-one 在 咪唑 、 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 20-epi-1α-[(tert-butyldimethylsilyl)oxy]-2β-[(trimethylsilyl)oxy]-22-oxa-25-[(triethylsilyl)oxy]-19-norvitamin D₃ tert-butyldimethylsilyl ether
  参考文献：
  名称：

  Synthesis and biological activities of new 1α,25-dihydroxy-19-norvitamin D3 analogs with modifications in both the A-ring and the side chain

  摘要：

  In a series of studies on structure-activity relationships of 2-substituted 19-norvitamin D analogs, we found that 1 alpha,25-dihydroxy-19-norvitamin D-3 analogs with 2 beta-hydroxyethoxy or 2E-hydroxyethylidene moieties show strong binding affinity for the vitamin D receptor (VDR) as well as marked transcriptional activity. To further examine the effects of side chain structure on the activity of 2-substituted 19-norvitamin D analogs, we have synthesized new 19-norvitamin D3 analogs with modifications in both the A-ring at the C(2) position and the side chain. The side chains of these analogs contained a double bond between C(22) and C(23) or an oxygen atom at C(22). The biological activity of the analogs was evaluated in vitro. All the side chain-modified analogs were less active than 1 alpha,25-dihydroxyvitamin D-3 1e and the parent compounds 3-6e possessing a natural 20R-configuration in binding to the VDR, but, except for the (20R)-22-oxa analogs 3-6d, were significantly more potent in transcriptional activity. Of the side-chain-modified analogs 4 and 5, the 2 beta-hydroxyethoxy- and 2E-hydroxyethylidene-22,24-diene-24a,26a,27a-trihorno analogs showed markedly higher transcriptional activity (25- and 17.5-fold, respectively) compared with le. Elongation of the side chain at the C-24, C-26, and C-27 positions and introduction of a 22,24-diene moiety strongly increased transcriptional activity, as seen in the 20-epi analogs 3-6f. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.01.061
• 作为产物：
  描述：

  toluene-4-sulfonic acid 3-[(tert-butyldimethylsilyl)oxy]-3-methylbutyl ester 在 四丙基高钌酸铵 、 4 A molecular sieve 、 sodium hydride 、 对甲苯磺酸 、 N-甲基吗啉氧化物 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 (20R)-de-A,B-25-hydroxy-22-oxacholestan-8-one
  参考文献：
  名称：

  Synthesis and biological activities of new 1α,25-dihydroxy-19-norvitamin D3 analogs with modifications in both the A-ring and the side chain

  摘要：

  In a series of studies on structure-activity relationships of 2-substituted 19-norvitamin D analogs, we found that 1 alpha,25-dihydroxy-19-norvitamin D-3 analogs with 2 beta-hydroxyethoxy or 2E-hydroxyethylidene moieties show strong binding affinity for the vitamin D receptor (VDR) as well as marked transcriptional activity. To further examine the effects of side chain structure on the activity of 2-substituted 19-norvitamin D analogs, we have synthesized new 19-norvitamin D3 analogs with modifications in both the A-ring at the C(2) position and the side chain. The side chains of these analogs contained a double bond between C(22) and C(23) or an oxygen atom at C(22). The biological activity of the analogs was evaluated in vitro. All the side chain-modified analogs were less active than 1 alpha,25-dihydroxyvitamin D-3 1e and the parent compounds 3-6e possessing a natural 20R-configuration in binding to the VDR, but, except for the (20R)-22-oxa analogs 3-6d, were significantly more potent in transcriptional activity. Of the side-chain-modified analogs 4 and 5, the 2 beta-hydroxyethoxy- and 2E-hydroxyethylidene-22,24-diene-24a,26a,27a-trihorno analogs showed markedly higher transcriptional activity (25- and 17.5-fold, respectively) compared with le. Elongation of the side chain at the C-24, C-26, and C-27 positions and introduction of a 22,24-diene moiety strongly increased transcriptional activity, as seen in the 20-epi analogs 3-6f. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.01.061