(3aR,7aS)-7a-methyl-1-[1-(4-methyl-4-trimethylsilanyloxy-3-oxopentyl)cyclopropyl]-3a,4,5,6,7,7a-hexahydro-3H-inden-4-one | 1143517-47-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (3aR,7aS)-7a-methyl-1-[1-(4-methyl-4-trimethylsilanyloxy-3-oxopentyl)cyclopropyl]-3a,4,5,6,7,7a-hexahydro-3H-inden-4-one
• 英文别名: (3aR,7aS)-7a-methyl-1-[1-(4-methyl-3-oxo-4-trimethylsilyloxypentyl)cyclopropyl]-3a,5,6,7-tetrahydro-3H-inden-4-one
• CAS: 1143517-47-8
• 化学式: C₂₂H₃₆O₃Si
• 分子量: 376.612
• InChiKey: BNQKVFORASPNSJ-KKSFZXQISA-N

物化性质

• 沸点：
  433.2±30.0 °C(predicted)
• 密度：
  1.043±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.45
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3aR,7aS)-7a-methyl-1-[1-(4-methyl-4-trimethylsilanyloxy-3-oxopentyl)cyclopropyl]-3a,4,5,6,7,7a-hexahydro-3H-inden-4-one 、 [3S-(1Z,3a,5b)]-[2-[3,5-二[(叔丁基)二甲基硅氧基]-2-亚甲基环己亚基]乙基]二苯基氧化膦 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 反应 3.67h， 以152 mg的产率得到1α,3β-di(tert-butyl-dimethyl-silanyloxy)-25-trimethylsilanyloxy-16-ene-20-cyclopropyl-24-oxo-cholecalciferol
  参考文献：
  名称：

  Synthesis and Anti-inflammatory Properties of 1α,25-Dihydroxy-16-ene-20-cyclopropyl-24-oxo-vitamin D₃, a Hypocalcemic, Stable Metabolite of 1α,25-Dihydroxy-16-ene-20-cyclopropyl-vitamin D₃

  摘要：

  1 alpha,25(OH)(2)-16-ene-20-cyclopropyl-vitamin D-3 (13) is several fold more potent than the natural hormone 1 alpha,25-dihydroxyvitamin D-3 (1) as an anti-infilammatory agent. Here, we have further analyzed the anti-inflammatory properties of 13, confirming it as the most potent analogue tested within this family. We then determined the structures of all the natural metabolites of 13, including the 24-oxo metabolite 14, and carried out its synthesis. A comparison of 13 with 14 showed a similar induction of the primary VDR target genes CYP24A1 and CAMP and comparable anti-inflammatory properties as revealed by a similar inhibition of TNF-alpha, IL-12/23p40, IL-6, and IFN-gamma production. Interestingly, 14 displays a 3-fold lower calcemic activity in vivo compared to 13. Collectively, these findings indicate that the strong potency of 13 can be explained by the accumulation of its stable 24-oxo metabolite, which shows immunoregulatory and anti-inflammatory properties superimposable, to those exerted by 13 itself.

  DOI：

  10.1021/jm801365a
• 作为产物：
  描述：

  在 三甲基硅咪唑 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以100 mg的产率得到(3aR,7aS)-7a-methyl-1-[1-(4-methyl-4-trimethylsilanyloxy-3-oxopentyl)cyclopropyl]-3a,4,5,6,7,7a-hexahydro-3H-inden-4-one
  参考文献：
  名称：

  Synthesis and Anti-inflammatory Properties of 1α,25-Dihydroxy-16-ene-20-cyclopropyl-24-oxo-vitamin D₃, a Hypocalcemic, Stable Metabolite of 1α,25-Dihydroxy-16-ene-20-cyclopropyl-vitamin D₃

  摘要：

  1 alpha,25(OH)(2)-16-ene-20-cyclopropyl-vitamin D-3 (13) is several fold more potent than the natural hormone 1 alpha,25-dihydroxyvitamin D-3 (1) as an anti-infilammatory agent. Here, we have further analyzed the anti-inflammatory properties of 13, confirming it as the most potent analogue tested within this family. We then determined the structures of all the natural metabolites of 13, including the 24-oxo metabolite 14, and carried out its synthesis. A comparison of 13 with 14 showed a similar induction of the primary VDR target genes CYP24A1 and CAMP and comparable anti-inflammatory properties as revealed by a similar inhibition of TNF-alpha, IL-12/23p40, IL-6, and IFN-gamma production. Interestingly, 14 displays a 3-fold lower calcemic activity in vivo compared to 13. Collectively, these findings indicate that the strong potency of 13 can be explained by the accumulation of its stable 24-oxo metabolite, which shows immunoregulatory and anti-inflammatory properties superimposable, to those exerted by 13 itself.

  DOI：

  10.1021/jm801365a

文献信息

• Synthesis and Anti-inflammatory Properties of 1α,25-Dihydroxy-16-ene-20-cyclopropyl-24-<i>oxo</i>-vitamin D₃, a Hypocalcemic, Stable Metabolite of 1α,25-Dihydroxy-16-ene-20-cyclopropyl-vitamin D₃
  作者：Gilles Laverny、Giuseppe Penna、Milan Uskokovic、Stanislaw Marczak、Hubert Maehr、Pawel Jankowski、Caroline Ceailles、Paul Vouros、Brenden Smith、Matthew Robinson、G. Satyanarayana Reddy、Luciano Adorini

  DOI：10.1021/jm801365a

  日期：2009.4.23

  1 alpha,25(OH)(2)-16-ene-20-cyclopropyl-vitamin D-3 (13) is several fold more potent than the natural hormone 1 alpha,25-dihydroxyvitamin D-3 (1) as an anti-infilammatory agent. Here, we have further analyzed the anti-inflammatory properties of 13, confirming it as the most potent analogue tested within this family. We then determined the structures of all the natural metabolites of 13, including the 24-oxo metabolite 14, and carried out its synthesis. A comparison of 13 with 14 showed a similar induction of the primary VDR target genes CYP24A1 and CAMP and comparable anti-inflammatory properties as revealed by a similar inhibition of TNF-alpha, IL-12/23p40, IL-6, and IFN-gamma production. Interestingly, 14 displays a 3-fold lower calcemic activity in vivo compared to 13. Collectively, these findings indicate that the strong potency of 13 can be explained by the accumulation of its stable 24-oxo metabolite, which shows immunoregulatory and anti-inflammatory properties superimposable, to those exerted by 13 itself.