(1R,3R)-3-(but-3'-enyloxy)-1-[(tert-butyldimethylsilyl)oxy]-5,5-ethylenedithio-2-methylenecyclohexane | 1155974-98-3

• 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: (1R,3R)-3-(but-3'-enyloxy)-1-[(tert-butyldimethylsilyl)oxy]-5,5-ethylenedithio-2-methylenecyclohexane
• 英文别名: [(7R,9R)-9-but-3-enoxy-8-methylidene-1,4-dithiaspiro[4.5]decan-7-yl]oxy-tert-butyl-dimethylsilane
• CAS: 1155974-98-3
• 化学式: C₁₉H₃₄O₂S₂Si
• 分子量: 386.695
• InChiKey: IOZSHBJTNMLBRR-IAGOWNOFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.86
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  69.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1R,3R)-3-(but-3'-enyloxy)-1-[(tert-butyldimethylsilyl)oxy]-5,5-ethylenedithio-2-methylenecyclohexane 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以100%的产率得到(1R,3R)-3-(but-3'-enyloxy)-5,5-ethylenedithio-2-methylenecyclohexanol
  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：

  4-溴-1-丁烯 、 (1R,3R)-3-[(tert-butyldimethylsilyl)oxy]-5,5-ethylenedithio-2-methylenecyclohexanol 在 18-冠醚-6 、 sodium hydride 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 反应 5.17h， 以39%的产率得到(1R,3R)-3-(but-3'-enyloxy)-1-[(tert-butyldimethylsilyl)oxy]-5,5-ethylenedithio-2-methylenecyclohexane
  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

文献信息

• 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
  作者：Agnieszka Glebocka、Katarzyna Sokolowska、Rafal R. Sicinski、Lori A. Plum、Hector F. DeLuca

  DOI：10.1021/jm9001583

  日期：2009.6.11

  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.