(3aR,7aS)-7a-Methyl-1-((R)-1,6,6-trimethyl-5-oxo-heptyl)-3,3a,5,6,7,7a-hexahydro-inden-4-one | 419572-80-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3aR,7aS)-7a-Methyl-1-((R)-1,6,6-trimethyl-5-oxo-heptyl)-3,3a,5,6,7,7a-hexahydro-inden-4-one
• 英文别名: (3aR,7aS)-1-[(2R)-7,7-dimethyl-6-oxooctan-2-yl]-7a-methyl-3a,5,6,7-tetrahydro-3H-inden-4-one
• CAS: 419572-80-8
• 化学式: C₂₀H₃₂O₂
• 分子量: 304.473
• InChiKey: QFQCKIJDTJWUGS-PTSWNOGYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3aR,7aS)-7a-Methyl-1-((R)-1,6,6-trimethyl-5-oxo-heptyl)-3,3a,5,6,7,7a-hexahydro-inden-4-one 在 吡啶 、 四丁基氟化铵 、 苯基锂 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 环己烷 为溶剂， 反应 59.33h， 生成 (R)-7-{(3aS,7aS)-4-[2-[(3S,5R)-3,5-Dihydroxy-2-methylene-cyclohex-(Z)-ylidene]-eth-(E)-ylidene]-7a-methyl-3a,4,5,6,7,7a-hexahydro-3H-inden-1-yl}-2,2-dimethyl-octan-3-one O-methyl-oxime
  参考文献：
  名称：

  Conceptually New Low-Calcemic Oxime Analogues of the Hormone 1α,25-Dihydroxyvitamin D₃:  Synthesis and Biological Testing

  摘要：

  New chemical entities 16-ene-25-ketone 2b and the corresponding oxime 3b and oxime ether 4b, analogues of natural calcitriol (1), were rationally designed and synthesized on a milligram scale. Chemical introduction of the oxime ether functionality in analogue 4b was successful via direct oximation of an intact vitamin D conjugated triene system. Even though all three analogues are at least as antiproliferative in vitro as calcitriol (1) even at physiologically relevant low nanomolar concentrations, only side chain ketone 2b is more transcriptionally potent than calcitriol (1). Although oxime O-methyl ether 4b lacks the traditional side chain hydrogen bond-donating OH group of the natural hormone and lacks also the oxime-NOH group of analogue 3b, surprisingly, oxime ether 4b retains 20% of the transcriptional potency of natural calcitriol (1). In terms of in vivo toxicity (hypercalcemia), ketone 2b is strongly calcemic in rats, whereas oxime 3b and oxime ether 4b are considerably less calcemic (i.e., safer) than calcitriol (1).

  DOI：

  10.1021/jm010560o
• 作为产物：
  描述：

  Triethyl-[(3aR,4S,7aS)-1-((R)-3-iodo-1-methyl-propyl)-7a-methyl-3a,4,5,6,7,7a-hexahydro-3H-inden-4-yloxy]-silane 在 六甲基磷酰三胺 、 四丙基高钌酸铵 、 四丁基氟化铵 、 N-甲基吗啉氧化物 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 19.25h， 生成 (3aR,7aS)-7a-Methyl-1-((R)-1,6,6-trimethyl-5-oxo-heptyl)-3,3a,5,6,7,7a-hexahydro-inden-4-one
  参考文献：
  名称：

  Conceptually New Low-Calcemic Oxime Analogues of the Hormone 1α,25-Dihydroxyvitamin D₃:  Synthesis and Biological Testing

  摘要：

  New chemical entities 16-ene-25-ketone 2b and the corresponding oxime 3b and oxime ether 4b, analogues of natural calcitriol (1), were rationally designed and synthesized on a milligram scale. Chemical introduction of the oxime ether functionality in analogue 4b was successful via direct oximation of an intact vitamin D conjugated triene system. Even though all three analogues are at least as antiproliferative in vitro as calcitriol (1) even at physiologically relevant low nanomolar concentrations, only side chain ketone 2b is more transcriptionally potent than calcitriol (1). Although oxime O-methyl ether 4b lacks the traditional side chain hydrogen bond-donating OH group of the natural hormone and lacks also the oxime-NOH group of analogue 3b, surprisingly, oxime ether 4b retains 20% of the transcriptional potency of natural calcitriol (1). In terms of in vivo toxicity (hypercalcemia), ketone 2b is strongly calcemic in rats, whereas oxime 3b and oxime ether 4b are considerably less calcemic (i.e., safer) than calcitriol (1).

  DOI：

  10.1021/jm010560o

文献信息

• Conceptually New Low-Calcemic Oxime Analogues of the Hormone 1α,25-Dihydroxyvitamin D₃:  Synthesis and Biological Testing
  作者：Gary H. Posner、Bethany A. Halford、Sara Peleg、Patrick Dolan、Thomas W. Kensler

  DOI：10.1021/jm010560o

  日期：2002.4.1

  New chemical entities 16-ene-25-ketone 2b and the corresponding oxime 3b and oxime ether 4b, analogues of natural calcitriol (1), were rationally designed and synthesized on a milligram scale. Chemical introduction of the oxime ether functionality in analogue 4b was successful via direct oximation of an intact vitamin D conjugated triene system. Even though all three analogues are at least as antiproliferative in vitro as calcitriol (1) even at physiologically relevant low nanomolar concentrations, only side chain ketone 2b is more transcriptionally potent than calcitriol (1). Although oxime O-methyl ether 4b lacks the traditional side chain hydrogen bond-donating OH group of the natural hormone and lacks also the oxime-NOH group of analogue 3b, surprisingly, oxime ether 4b retains 20% of the transcriptional potency of natural calcitriol (1). In terms of in vivo toxicity (hypercalcemia), ketone 2b is strongly calcemic in rats, whereas oxime 3b and oxime ether 4b are considerably less calcemic (i.e., safer) than calcitriol (1).