(20S,22R)-1α,3β-bis(methoxycarbonyloxy)-22-butyl-24-hydroxy-25-[(methoxymethyl)oxy]cholesta-5,7-diene | 213312-45-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (20S,22R)-1α,3β-bis(methoxycarbonyloxy)-22-butyl-24-hydroxy-25-[(methoxymethyl)oxy]cholesta-5,7-diene
• 英文别名: [(1S,3R,9S,10R,13R,14R,17R)-17-[(2S,3R)-3-butyl-5-hydroxy-6-(methoxymethoxy)-6-methylheptan-2-yl]-1-methoxycarbonyloxy-10,13-dimethyl-2,3,4,9,11,12,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-yl] methyl carbonate
• CAS: 213312-45-9
• 化学式: C₃₇H₆₀O₉
• 分子量: 648.878
• InChiKey: QSSFTVRDAQOKHO-RPFHTLSJSA-N

物化性质

• 沸点：
  717.4±60.0 °C(predicted)
• 密度：
  1.12±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.6
• 重原子数：
  46
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (20S,22R)-1α,3β-bis(methoxycarbonyloxy)-22-butyl-24-hydroxy-25-[(methoxymethyl)oxy]cholesta-5,7-diene 在 咪唑 、 偶氮二异丁腈 、 三正丁基氢锡 、 sodium hydride 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 20.0h， 生成 (20S,22R)-1α,3β-bis(methoxycarbonyloxy)-22-butyl-25-[(methoxymethyl)oxy]cholesta-5,7-diene
  参考文献：
  名称：

  22-Alkyl-20-epi-1α,25-dihydroxyvitamin D₃ Compounds of Superagonistic Activity:  Syntheses, Biological Activities and Interaction with the Receptor

  摘要：

  We previously reported that 22R-methyl-20-epi-1,25-(OH)(2)D-3 (3) possesses strong binding affinity for the vitamin D receptor (VDR) and shows superagonistic biological activities. To examine the effect of the length of an alkyl substituent at C(22) and to extend our compound library, we successfully synthesized 22R-ethyl-20-epi-1,25-(OH)(2)D-3 (4) and 22R-butyl-20-epi-1,25-(OH)(2)D-3 (5). Surprisingly, 22-ethyl analogue 4 showed stronger VDR binding affinity and transactivation potency than the superagonist of methyl analogue 3, but its calcemic activity in vivo was weaker than that of both the methyl analogue 3 and the natural hormone (1), while 22-butyl analogue 5 showed activities comparable to those of the hormone (1). A study of the docking of these new analogues to the VDR-LBD and alanine scanning mutational analysis demonstrated that 22-methyl and 22-ethyl substituents enhance the favorable hydrophobic interactions with residues lining the ligand binding pocket of the VDR, and that 22-butyl analogue 5 binds to the VDR by an induced fit mechanism.

  DOI：

  10.1021/jm060889f
• 作为产物：
  描述：

  [(1S,3R,9S,10R,13R,14R,17R)-1-methoxycarbonyloxy-17-[(Z,2S)-6-(methoxymethoxy)-6-methyl-5-oxohept-3-en-2-yl]-10,13-dimethyl-2,3,4,9,11,12,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-yl] methyl carbonate 在 sodium tetrahydroborate 、 copper(I) bromide dimethylsulfide complex 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.42h， 生成 (20S,22R)-1α,3β-bis(methoxycarbonyloxy)-22-butyl-24-hydroxy-25-[(methoxymethyl)oxy]cholesta-5,7-diene
  参考文献：
  名称：

  22-Alkyl-20-epi-1α,25-dihydroxyvitamin D₃ Compounds of Superagonistic Activity:  Syntheses, Biological Activities and Interaction with the Receptor

  摘要：

  We previously reported that 22R-methyl-20-epi-1,25-(OH)(2)D-3 (3) possesses strong binding affinity for the vitamin D receptor (VDR) and shows superagonistic biological activities. To examine the effect of the length of an alkyl substituent at C(22) and to extend our compound library, we successfully synthesized 22R-ethyl-20-epi-1,25-(OH)(2)D-3 (4) and 22R-butyl-20-epi-1,25-(OH)(2)D-3 (5). Surprisingly, 22-ethyl analogue 4 showed stronger VDR binding affinity and transactivation potency than the superagonist of methyl analogue 3, but its calcemic activity in vivo was weaker than that of both the methyl analogue 3 and the natural hormone (1), while 22-butyl analogue 5 showed activities comparable to those of the hormone (1). A study of the docking of these new analogues to the VDR-LBD and alanine scanning mutational analysis demonstrated that 22-methyl and 22-ethyl substituents enhance the favorable hydrophobic interactions with residues lining the ligand binding pocket of the VDR, and that 22-butyl analogue 5 binds to the VDR by an induced fit mechanism.

  DOI：

  10.1021/jm060889f