(1R,3aR,7aR)-1-[(1R,4S)-4,5-di(tert-butyldimethylsilyloxy)-1,5-dimethylhexyl]-7a-methyloctahydro-1H-inden-4-one | 239100-30-2

• 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: (1R,3aR,7aR)-1-[(1R,4S)-4,5-di(tert-butyldimethylsilyloxy)-1,5-dimethylhexyl]-7a-methyloctahydro-1H-inden-4-one
• 英文别名: (1R,3aR,4S,7aR)-1-[(1R,4S)-4,5-di(tert-butyldimethylsilyloxy)-1,5-dimethylhexyl]-7a-methyloctahydro-1H-inden-4-one；(1R,3aR,7aR)-1-[(2R,5S)-5,6-bis[[tert-butyl(dimethyl)silyl]oxy]-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-one
• CAS: 239100-30-2
• 化学式: C₃₀H₆₀O₃Si₂
• 分子量: 524.976
• InChiKey: BJPLJYXKSZJCKB-SEZGZLGISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.38
• 重原子数：
  35
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,3aR,7aR)-1-[(1R,4S)-4,5-di(tert-butyldimethylsilyloxy)-1,5-dimethylhexyl]-7a-methyloctahydro-1H-inden-4-one 在 四(三苯基膦)钯 sodium hexamethyldisilazane 、 三乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 2.0h， 生成 1α,2β,3β-tris(triethylsilyloxy)-24S,25-di(tert-butyldimethylsilyloxy)-9,10-secocholesta-5,7,10(19)-triene
  参考文献：
  名称：

  Synthesis of putative metabolites of 1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3 (ED-71)

  摘要：

  1 alpha,25-Dihydroxy-2 beta-(3-hydroxypropoxy)vitamin D-3 (ED-71), an analog of active vitamin D-3, 1 alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] is under phase III clinical trials in Japan for the treatment of osteoporosis and bone fracture prevention. Since ED-71 has a substituent at the 2 beta-position of the A-ring, it is recognized that the metabolic pathway of ED-71 might be more complicated than 1,25(OH)(2)D-3 because of metabolism at the 2 beta-position substituent in addition to the inherent metabolism of the side chain. To clarify the metabolism of hydroxypropoxy substituent of the 2 beta-positon and a combination of metabolism between side chain and 2 beta-positon, four putative metabolites of ED-71 have been prepared as authentic samples. The metabolites at the 2 beta-positon, the methyl ester derivative considered as an ester standard of the oxidized metabolite and the tetraol derivative as the truncated metabolite were synthesized from alpha-epoxide, a key intermediate of ED-71 synthesis. The combination metabolites between side chain and 2 beta-positon, the 24(S)- and 24(R)-pentaols were synthesized using Trost's convergent method. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2005.11.001
• 作为产物：
  描述：

  (S)-2-((3R,3aR,7S,7aR)-octahydro-7-hydroxy-3a-methyl-1H-inden-3-yl)propyl 4-methylbenzenesulfonate 在 咪唑 、 2,6-二甲基吡啶 、 盐酸 、 lithium aluminium tetrahydride 、 正丁基锂 、 4 A molecular sieve 、 N-甲基吗啉氧化物 、 sodium iodide 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 49.0h， 生成 (1R,3aR,7aR)-1-[(1R,4S)-4,5-di(tert-butyldimethylsilyloxy)-1,5-dimethylhexyl]-7a-methyloctahydro-1H-inden-4-one
  参考文献：
  名称：

  Synthesis of putative metabolites of 1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3 (ED-71)

  摘要：

  1 alpha,25-Dihydroxy-2 beta-(3-hydroxypropoxy)vitamin D-3 (ED-71), an analog of active vitamin D-3, 1 alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] is under phase III clinical trials in Japan for the treatment of osteoporosis and bone fracture prevention. Since ED-71 has a substituent at the 2 beta-position of the A-ring, it is recognized that the metabolic pathway of ED-71 might be more complicated than 1,25(OH)(2)D-3 because of metabolism at the 2 beta-position substituent in addition to the inherent metabolism of the side chain. To clarify the metabolism of hydroxypropoxy substituent of the 2 beta-positon and a combination of metabolism between side chain and 2 beta-positon, four putative metabolites of ED-71 have been prepared as authentic samples. The metabolites at the 2 beta-positon, the methyl ester derivative considered as an ester standard of the oxidized metabolite and the tetraol derivative as the truncated metabolite were synthesized from alpha-epoxide, a key intermediate of ED-71 synthesis. The combination metabolites between side chain and 2 beta-positon, the 24(S)- and 24(R)-pentaols were synthesized using Trost's convergent method. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2005.11.001

文献信息

• Synthesis and biological characterization of 1α,24,25-trihydroxy-2β-(3-hydroxypropoxy)vitamin D3 (24-hydroxylated ED-71)
  作者：Susumi Hatakeyama、Akira Kawase、Yasushi Uchiyama、Junji Maeyama、Yoshiharu Iwabuchi、Noboru Kubodera

  DOI：10.1016/s0039-128x(00)00149-5

  日期：2001.3

  24-Hydroxylated derivatives were synthesized in 24(R) and 24(S) forms by the convergent method as analogs related to 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3). In the convergent synthesis, the A-ring fragment, synthesized from diethyl D-tartarate, and the C/D-ring fragments in 24(R) and 24(S) forms (vitamin D numbering), obtained from vitamin D(2) via the Inhoffen-Lythgoe diol, were

  通过会聚方法以24（R）和24（S）形式合成24-羟基衍生物，作为与1α，25-二羟基-2β-（3-羟基丙氧基）维生素D（3）相关的类似物。在收敛性合成中，由D-酒石酸二乙酯合成的A环片段和24（R）和24（S）形式的C / D环片段（维生素D编号）从维生素D（2）获得通过Inhoffen-Lythgoe二醇，以中等收率偶联，得到1alpha，24（R），25-三羟基-2beta-（3-羟基丙氧基）维生素D（3）和1alpha，24（S），25-三羟基-2beta -（3-羟基丙氧基）维生素D（3）。在初步的生物学评估中，与母体化合物相比，1alpha，25-dihydroxy-2beta-（3-hydroxypropoxy）维生素D（3）的24-羟基化导致对维生素D结合蛋白的体外亲和力减弱，体内钙化活性降低。
• Synthesis of putative metabolites of 1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3 (ED-71)
  作者：Yoshiyuki Ono、Hiroyoshi Watanabe、Ikuo Taira、Keisuke Takahashi、Jun Ishihara、Susumi Hatakeyama、Noboru Kubodera

  DOI：10.1016/j.steroids.2005.11.001

  日期：2006.7

  1 alpha,25-Dihydroxy-2 beta-(3-hydroxypropoxy)vitamin D-3 (ED-71), an analog of active vitamin D-3, 1 alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] is under phase III clinical trials in Japan for the treatment of osteoporosis and bone fracture prevention. Since ED-71 has a substituent at the 2 beta-position of the A-ring, it is recognized that the metabolic pathway of ED-71 might be more complicated than 1,25(OH)(2)D-3 because of metabolism at the 2 beta-position substituent in addition to the inherent metabolism of the side chain. To clarify the metabolism of hydroxypropoxy substituent of the 2 beta-positon and a combination of metabolism between side chain and 2 beta-positon, four putative metabolites of ED-71 have been prepared as authentic samples. The metabolites at the 2 beta-positon, the methyl ester derivative considered as an ester standard of the oxidized metabolite and the tetraol derivative as the truncated metabolite were synthesized from alpha-epoxide, a key intermediate of ED-71 synthesis. The combination metabolites between side chain and 2 beta-positon, the 24(S)- and 24(R)-pentaols were synthesized using Trost's convergent method. (c) 2006 Elsevier Inc. All rights reserved.