(1R,3R)-3-(but-3'-enyloxy)-5,5-ethylenedithio-2-methylenecyclohexanol | 1155975-26-0

• 英文名称: (1R,3R)-3-(but-3'-enyloxy)-5,5-ethylenedithio-2-methylenecyclohexanol
• 英文别名: (7R,9R)-7-but-3-enoxy-8-methylidene-1,4-dithiaspiro[4.5]decan-9-ol
• CAS: 1155975-26-0
• 化学式: C₁₃H₂₀O₂S₂
• 分子量: 272.433
• InChiKey: POJJVEQZMIFAFP-VXGBXAGGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  80.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1R,3R)-3-(but-3'-enyloxy)-5,5-ethylenedithio-2-methylenecyclohexanol 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 作用下， 以 甲苯 为溶剂， 反应 0.67h， 以93%的产率得到(5R,8aR)-7,7-ethylenedithio-2,3,5,6,8,8a-hexahydro-2H-chromen-5-ol
  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：

  (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