16,17-epoxy-4,9,13,17-tetramethyl-4(E),8(E),12(E)-octadecatrienyl methanesulfonate | 162132-22-1

• 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: 16,17-epoxy-4,9,13,17-tetramethyl-4(E),8(E),12(E)-octadecatrienyl methanesulfonate
• CAS: 162132-22-1
• 化学式: C₂₃H₄₀O₄S
• 分子量: 412.634
• InChiKey: DZOHVHQSHOEOCE-IVZDNUCCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  28.0
• 可旋转键数：
  14.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  55.9
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  16,17-epoxy-4,9,13,17-tetramethyl-4(E),8(E),12(E)-octadecatrienyl methanesulfonate 在 sodium hydroxide 、 oxone 、 四正辛基溴化铵 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 10.03h， 生成 16,17-epoxy-4,9,13,17-tetramethyl-4(E),8(E),12(E)-octadecatetraenyl 4'-methylpent-3'-enyl sulfoxide
  参考文献：
  名称：

  Synthesis of Sulfur- and Sulfoxide-Substituted 2,3-Oxidosqualenes and Their Evaluation as Inhibitors of 2,3-Oxidosqualene-Lanosterol Cyclase

  摘要：

  2,3-Oxidosqualene (23-OS) analogs that contain thioether (52-55) and sulfoxide (56-60) at positions normally occupied by carbons considered to be cationic during 2,3-oxidosqualene-lanosterol cyclase (OSC) cyclization (C-6, C-10, C-14, and C-19) were synthesized and tested as substrate mimic inhibitors of fungal and mammalian OSC. The analogs were found to be potent inhibitors of cyclase in cell-free extracts of Candida albicans and rat liver. Thioether analogs were more potent than the corresponding sulfoxides. In both series, those 2,3-OS analogs containing a sulfur at the position normally occupied by C-19 were the most potent. With C. albicans cyclase, the IC50 for thioether 55 was 0.0023 mu M while 60 exhibited an IC50 of 0.065 mu M, which are the lowest values reported for a inhibitor of this enzyme. Similarly, thioether 55 displayed an IC50 of 0.00082 mu M for rat liver cyclase which is the best inhibitor up to date for this enzyme. These results suggest that mimics with modification in the region of C-19 of 2,3-OS have a high affinity for the active site of these enzymes. The same series of analogs (52-60) were also tested for inhibition of cholesterol biosynthesis in intact MDBK (Madin Darbin bovine kidney) cells and for in vitro antifungal activity against C. albicans.

  DOI：

  10.1021/ja00107a011
• 作为产物：
  描述：

  4,9,13,17-tetranmethyloctadeca-4(E),8(E),12(E),16-tetraenyl tert-butyldimethylsilyl ether 在 N-溴代丁二酰亚胺(NBS) 、 四丁基氟化铵 、 水 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 72.0h， 生成 16,17-epoxy-4,9,13,17-tetramethyl-4(E),8(E),12(E)-octadecatrienyl methanesulfonate
  参考文献：
  名称：

  Synthesis of Sulfur- and Sulfoxide-Substituted 2,3-Oxidosqualenes and Their Evaluation as Inhibitors of 2,3-Oxidosqualene-Lanosterol Cyclase

  摘要：

  2,3-Oxidosqualene (23-OS) analogs that contain thioether (52-55) and sulfoxide (56-60) at positions normally occupied by carbons considered to be cationic during 2,3-oxidosqualene-lanosterol cyclase (OSC) cyclization (C-6, C-10, C-14, and C-19) were synthesized and tested as substrate mimic inhibitors of fungal and mammalian OSC. The analogs were found to be potent inhibitors of cyclase in cell-free extracts of Candida albicans and rat liver. Thioether analogs were more potent than the corresponding sulfoxides. In both series, those 2,3-OS analogs containing a sulfur at the position normally occupied by C-19 were the most potent. With C. albicans cyclase, the IC50 for thioether 55 was 0.0023 mu M while 60 exhibited an IC50 of 0.065 mu M, which are the lowest values reported for a inhibitor of this enzyme. Similarly, thioether 55 displayed an IC50 of 0.00082 mu M for rat liver cyclase which is the best inhibitor up to date for this enzyme. These results suggest that mimics with modification in the region of C-19 of 2,3-OS have a high affinity for the active site of these enzymes. The same series of analogs (52-60) were also tested for inhibition of cholesterol biosynthesis in intact MDBK (Madin Darbin bovine kidney) cells and for in vitro antifungal activity against C. albicans.

  DOI：

  10.1021/ja00107a011