4,4-dimethyl-14α-(prop-2-enyl)-5α-cholest-7-en-3β-ol | 119288-20-9

• 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: 4,4-dimethyl-14α-(prop-2-enyl)-5α-cholest-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-prop-2-enyl-2,3,5,6,9,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-ol
• CAS: 119288-20-9
• 化学式: C₃₂H₅₄O
• 分子量: 454.78
• InChiKey: ZMDRTFKNUOKDLB-SWOUMNRASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.2
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4,4-dimethyl-14α-(prop-2-enyl)-5α-cholest-7-en-3β-ol 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 18.0h， 以86%的产率得到4,4-dimethyl-14α-propyl-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：

  (2'R)-32-thiiranyllanost-7-en-3β-ol 在 三苯基膦 作用下， 以 甲苯 为溶剂， 反应 12.0h， 以89%的产率得到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

文献信息

• 14,15-Substituted lanosterols and their use as hypocholesterolemic agents
  申请人：THE DU PONT MERCK PHARMACEUTICAL COMPANY

  公开号：EP0276823A2

  公开（公告）日：1988-08-03

  Lanosterols substituted in the 14 and/or 15 position(s) which are active in inhibiting lanosta-8,24-dien-3β-ol 14α-methyl-demethylase activity, supressing 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity, decreasing cholesterol synthesis and reducing serum cholesterol levels are disclosed.

  公开了在 14 和/或 15 位被取代的羊毛甾醇，它们在抑制羊毛甾-8,24-二烯-3β-醇 14α-甲基-脱甲基酶活性、抑制 3-羟基-3-甲基戊二酰辅酶 A 还原酶 (HMGR) 活性、减少胆固醇合成和降低血清胆固醇水平方面具有活性。
• US5034548A
  申请人：——

  公开号：US5034548A

  公开（公告）日：1991-07-23
• US5041432A
  申请人：——

  公开号：US5041432A

  公开（公告）日：1991-08-20