tert-Butyl-((1S,3aR,4S,7aR)-1-iodoethynyl-7a-methyl-octahydro-inden-4-yloxy)-dimethyl-silane | 627461-23-8

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: tert-Butyl-((1S,3aR,4S,7aR)-1-iodoethynyl-7a-methyl-octahydro-inden-4-yloxy)-dimethyl-silane
• CAS: 627461-23-8
• 化学式: C₁₈H₃₁IOSi
• 分子量: 418.434
• InChiKey: MKJJGMPYGOSZSD-MUQADHOPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.99
• 重原子数：
  21.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  9.23
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  tert-Butyl-((1S,3aR,4S,7aR)-1-iodoethynyl-7a-methyl-octahydro-inden-4-yloxy)-dimethyl-silane 在 哌啶 、 copper(l) iodide 、 camphor-10-sulfonic acid 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 55.0h， 生成 1α,2ξ-dihydroxy-24-trimethylsilyl-20,20,22,22,23,23,24,24-octadehydro-19,21,25,26,27-pentanorvitamin D₃ 1,3-bis-tert-butyldimethylsilyl-2-trimethylsilyl ether
  参考文献：
  名称：

  Synthesis, Biological Activities, and X-ray Crystal Structural Analysis of 25-Hydroxy-25(or 26)-adamantyl-17-[20(22),23-diynyl]-21-norvitamin D Compounds

  摘要：

  Novel 19-norvitamin D analogues (ADYW1-4, 5a-d) in which an adamantyl diyne side chain is attached directly to the 17-position of the D:ring are designed and steroselectively synthesized: The adamantane ring of these analogues was expected to interfere with helix 12 (H12, activation function:) of the vitamin D receptor (VDR) to modulate its activities. The analogue 5b binds to the VDR (7% of the natural hormone) and shows significant partial agonistic activity in transactivation assay. Compound 5b showed Considerable selectivity in VDR target genes expressions in vitro, it was taken up by target cells 2-3 times more readily, and its lifetime was three times longer than the natural hormone. The X-ray crystal Structure of 5b in complex with VDR reveals that the ligand binds similarly to the natural hormone, but the diyne moiety is slightly bent (angles around the diyne 5 degrees to 8 degrees) with respect to the original diyne vitamin D compound 6 6 in VDR (<1 degrees) due to steric hindrance with helix 12.

  DOI：

  10.1021/acs.jmedchem.5b00792
• 作为产物：
  描述：

  tert-Butyl-((1R,3aR,4S,7aR)-1-ethynyl-7a-methyl-octahydro-inden-4-yloxy)-dimethyl-silane 在 碘 、 正己基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 0.25h， 以86%的产率得到tert-Butyl-((1S,3aR,4S,7aR)-1-iodoethynyl-7a-methyl-octahydro-inden-4-yloxy)-dimethyl-silane
  参考文献：
  名称：

  The First Locked Side-Chain Analogues of Calcitriol (1α,25-Dihydroxyvitamin D₃) Induce Vitamin D Receptor Transcriptional Activity

  摘要：

  [GRAPHIC]We describe the synthesis of the first locked side-chain analogues of the natural hormone 1alpha,25-(OH)(2)-D-3 and their effects on gene transcription in human colon cancer cells. Analogue 2 was more potent than 1alpha,25-(OH)(2)-D-3 at inducing vitamin D receptor (VDR) transcriptional activity. Analogues 3a and 3b show potency similar to that of 1alpha,25-(OH)(2)-D-3, whereas 3c was less active. The novel analogues efficiently bind VDR in vivo to induce transcription from a consensus vitamin D responsive element (VDRE).

  DOI：

  10.1021/ol0351246