(5R,7R,9R)-7-[(tert-butyldimethylsilyl)oxy]-2,2-dimethyl-1,3-dioxa-8,8-ethylenedithio-9-hydroxyspiro[4.5]decane | 1155975-09-9

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫代缩醛
• 英文名称: (5R,7R,9R)-7-[(tert-butyldimethylsilyl)oxy]-2,2-dimethyl-1,3-dioxa-8,8-ethylenedithio-9-hydroxyspiro[4.5]decane
• 英文别名: (5R,7R,13R)-13-[tert-butyl(dimethyl)silyl]oxy-3,3-dimethyl-2,4-dioxa-9,12-dithiadispiro[4.2.48.25]tetradecan-7-ol
• CAS: 1155975-09-9
• 化学式: C₁₈H₃₄O₄S₂Si
• 分子量: 406.683
• InChiKey: SNUIXJBYTJPRHC-CKEIUWERSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.23
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  98.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (5R,7R,9R)-7-[(tert-butyldimethylsilyl)oxy]-2,2-dimethyl-1,3-dioxa-8,8-ethylenedithio-9-hydroxyspiro[4.5]decane 、 3-溴丙烯 在 18-冠醚-6 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.58h， 以95%的产率得到(5R,7R,9R)-9-allyloxy-7-[(tert-butyldimethylsilyl)oxy]-2,2-dimethyl-1,3-dioxa-8,8-ethylenedithiospiro[4.5]decane
  参考文献：
  名称：

  New 1α,25-Dihydroxy-19-norvitamin D₃ Compounds Constrained in a Single A-Ring Conformation: Synthesis of the Analogues by Ring-Closing Metathesis Route and Their Biological Evaluation

  摘要：

  Vitamin D compounds possessing A rings prohibited from flipping to the alternative chair form (i.e., analogues 2 and 26) were synthesized. The bicyclic fragment 22 consisting of the fused cyclohexane and dihydropyran rings was constructed via the ring-closing metathesis route. Also, a homologous synthon 23 with an attached dihydropyran ring was successfully synthesized using this strategy. The carbonyl deprotection in 22 yielded cyclohexanone 5 that was subjected to Julia coupling with the anion of the phenylthiazoline sulfone 25. In the resulting isomeric 19-norvitamins 2 and 26, their A rings can exist only in the alpha- and beta-conformation. The analogue 26 was 300 times more active in binding to the vitamin D receptor protein, 30 times more effective in causing HL-60 differentiation, and 10 times more active in transcription. These results confirm that the beta-chair form of the vitamin D ring A is necessary for the binding to the receptor.

  DOI：

  10.1021/jm9001583
• 作为产物：
  描述：

  (1'R,3'R,5'R)-3'-[(tert-butyldimethylsilyl)oxy]-1',5'-dihydroxy-4,4-ethylenedithiomethanol 、 2,2-二甲氧基丙烷 在 对甲苯磺酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 以76%的产率得到(5R,7R,9R)-7-[(tert-butyldimethylsilyl)oxy]-2,2-dimethyl-1,3-dioxa-8,8-ethylenedithio-9-hydroxyspiro[4.5]decane
  参考文献：
  名称：

  New 1α,25-Dihydroxy-19-norvitamin D₃ Compounds Constrained in a Single A-Ring Conformation: Synthesis of the Analogues by Ring-Closing Metathesis Route and Their Biological Evaluation

  摘要：

  Vitamin D compounds possessing A rings prohibited from flipping to the alternative chair form (i.e., analogues 2 and 26) were synthesized. The bicyclic fragment 22 consisting of the fused cyclohexane and dihydropyran rings was constructed via the ring-closing metathesis route. Also, a homologous synthon 23 with an attached dihydropyran ring was successfully synthesized using this strategy. The carbonyl deprotection in 22 yielded cyclohexanone 5 that was subjected to Julia coupling with the anion of the phenylthiazoline sulfone 25. In the resulting isomeric 19-norvitamins 2 and 26, their A rings can exist only in the alpha- and beta-conformation. The analogue 26 was 300 times more active in binding to the vitamin D receptor protein, 30 times more effective in causing HL-60 differentiation, and 10 times more active in transcription. These results confirm that the beta-chair form of the vitamin D ring A is necessary for the binding to the receptor.

  DOI：

  10.1021/jm9001583