(2'S)-32-thiiranyllanost-7-en-3β-ol | 131407-07-3

• 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: (2'S)-32-thiiranyllanost-7-en-3β-ol
• 英文别名: (3S,5R,9R,10R,13R,14S,17R)-4,4,10,13-tetramethyl-17-[(2R)-6-methylheptan-2-yl]-14-[[(2S)-thiiran-2-yl]methyl]-2,3,5,6,9,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-ol
• CAS: 131407-07-3
• 化学式: C₃₂H₅₄OS
• 分子量: 486.846
• InChiKey: WUZAFKXNLIDISX-GTQDKQNRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  45.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2'S)-32-thiiranyllanost-7-en-3β-ol 在 三苯基膦 作用下， 以 甲苯 为溶剂， 反应 12.0h， 生成 4,4-dimethyl-14α-(prop-2-enyl)-5α-cholest-7-en-3β-ol
  参考文献：
  名称：

  Assessment of the active-site requirements of lanosterol 14.alpha.-demethylase: evaluation of novel substrate analogs as competitive inhibitors

  摘要：

  Lanosterol 14-alpha-demethylase (P450(14DM)), a cytochrome P450 enzyme, is responsible for the first stage in the biosynthesis of cholesterol (1) from lanosterol (2). Inhibitors of P450(14DM) may have therapeutic use in the treatment of familial hypercholesterolemia or as antifungal agents. The specificity of P450(14DM) has been investigated by using substrate analogues modified at the C-32 carbon. The hitherto undescribed 14-alpha-ethyl and 14-alpha-propyl analogues 15 and 13 of lanost-7-en-3-beta-ol, as well as the 14-alpha-ethenyl and 14-alpha-prop-2-enyl analogues 14 and 12, have been synthesized. These all proved to be good competitive inhibitors of the enzyme. A series of 32-oxiranes and 32-thiiranes was then synthesized and evaluated as inhibitors. Oxiranes 4 and 5 were excellent stereoselective competitive inhibitors of P450(14DM). The (2'S)-32-oxirane 4 had K(i) = 0.62-mu-M, and the (2'R)-32-oxirane 5 showed K(i) = 2-mu-M. The (2'R)-32-thiiranyl and (2'S)-32-thiiranyl compounds 10 and 11 were considerably less potent inhibitors. Comparison of the K(i) values for analogues 12-15, also good competitive inhibitors of this enzyme, indicated the P450(14DM) active site to be relatively insensitive to the size and degree of unsaturation of C-14-alpha alkyl substituents up to and including propyl.

  DOI：

  10.1021/jo00003a059
• 作为产物：
  描述：

  32-formyllanost-7-en-3β-ol 在 sodium hydride 、 三苯基瞵硫 、 三氟乙酸 作用下， 以 苯 为溶剂， 反应 17.08h， 生成 (2'S)-32-thiiranyllanost-7-en-3β-ol
  参考文献：
  名称：

  Assessment of the active-site requirements of lanosterol 14.alpha.-demethylase: evaluation of novel substrate analogs as competitive inhibitors

  摘要：

  Lanosterol 14-alpha-demethylase (P450(14DM)), a cytochrome P450 enzyme, is responsible for the first stage in the biosynthesis of cholesterol (1) from lanosterol (2). Inhibitors of P450(14DM) may have therapeutic use in the treatment of familial hypercholesterolemia or as antifungal agents. The specificity of P450(14DM) has been investigated by using substrate analogues modified at the C-32 carbon. The hitherto undescribed 14-alpha-ethyl and 14-alpha-propyl analogues 15 and 13 of lanost-7-en-3-beta-ol, as well as the 14-alpha-ethenyl and 14-alpha-prop-2-enyl analogues 14 and 12, have been synthesized. These all proved to be good competitive inhibitors of the enzyme. A series of 32-oxiranes and 32-thiiranes was then synthesized and evaluated as inhibitors. Oxiranes 4 and 5 were excellent stereoselective competitive inhibitors of P450(14DM). The (2'S)-32-oxirane 4 had K(i) = 0.62-mu-M, and the (2'R)-32-oxirane 5 showed K(i) = 2-mu-M. The (2'R)-32-thiiranyl and (2'S)-32-thiiranyl compounds 10 and 11 were considerably less potent inhibitors. Comparison of the K(i) values for analogues 12-15, also good competitive inhibitors of this enzyme, indicated the P450(14DM) active site to be relatively insensitive to the size and degree of unsaturation of C-14-alpha alkyl substituents up to and including propyl.

  DOI：

  10.1021/jo00003a059