lanost-7-ene-3β,32-diol 3β-acetate | 52648-02-9

• 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: lanost-7-ene-3β,32-diol 3β-acetate
• 英文别名: 3β-acetoxylanost-7-en-32-ol；[(3S,5R,9R,10R,13R,14S,17R)-14-(hydroxymethyl)-4,4,10,13-tetramethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,5,6,9,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-yl] acetate
• CAS: 52648-02-9
• 化学式: C₃₂H₅₄O₃
• 分子量: 486.779
• InChiKey: VKGPQFMXGUIFAY-GQPHDMOOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.8
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  lanost-7-ene-3β,32-diol 3β-acetate 在 (diethylamino)sulfur difluoride 、 silver carbonate 作用下， 以 苯 为溶剂， 反应 6.5h， 生成 Acetic acid (3S,5S,9R,10R,13R,14S,17R)-14-difluoromethyl-17-((R)-1,5-dimethyl-hexyl)-4,4,10,13-tetramethyl-2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl ester
  参考文献：
  名称：

  Synthesis of potential mechanism-based inactivators of lanosterol 14.alpha.-methyl demethylase

  摘要：

  DOI：

  10.1021/jo00292a037
• 作为产物：
  描述：

  Acetic acid (10R,13R,14S)-3-acetoxy-17-(1,5-dimethyl-hexyl)-4,4,10,13-tetramethyl-1,2,3,4,5,6,9,10,11,12,13,15,16,17-tetradecahydro-cyclopenta[a]phenanthren-14-ylmethyl ester 在 吡啶 、 4-二甲氨基吡啶 、 氢氧化钾 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 130.0h， 生成 lanost-7-ene-3β,32-diol 3β-acetate
  参考文献：
  名称：

  Synthesis of potential mechanism-based inactivators of lanosterol 14.alpha.-methyl demethylase

  摘要：

  DOI：

  10.1021/jo00292a037

文献信息

• FRYE, LEAH L.;ROBINSON, CECIL H., J. ORG. CHEM., 55,(1990) N, C. 1579-1584
  作者：FRYE, LEAH L.、ROBINSON, CECIL H.

  DOI：——

  日期：——
• TUCK, STEPHEN F.;ROBINSON, CECIL H.;SILVERTON, J. V., J. ORG. CHEM., 56,(1991) N, C. 1260-1266
  作者：TUCK, STEPHEN F.、ROBINSON, CECIL H.、SILVERTON, J. V.

  DOI：——

  日期：——
• Assessment of the active-site requirements of lanosterol 14.alpha.-demethylase: evaluation of novel substrate analogs as competitive inhibitors
  作者：Stephen F. Tuck、Cecil H. Robinson、J. V. Silverton

  DOI：10.1021/jo00003a059

  日期：1991.2

  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.