3,7b,11,11,13a,13b-hexamethyl-1,2,2a1,6a,7,7a,7b,8,9,10,11,11a,12,13,13a, 13b-hexadecahydronaphtho[20,10:4,5]indeno[7,1-de][1,3]dioxepin-10-ol

• 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: 3,7b,11,11,13a,13b-hexamethyl-1,2,2a1,6a,7,7a,7b,8,9,10,11,11a,12,13,13a, 13b-hexadecahydronaphtho[20,10:4,5]indeno[7,1-de][1,3]dioxepin-10-ol
• 英文别名: (1R,2R,5R,7S,10R,11R,13R,21S)-1,2,6,6,10,17-hexamethyl-14,16-dioxapentacyclo[11.7.1.02,11.05,10.018,21]henicos-17-en-7-ol
• 化学式: C₂₅H₄₀O₃
• 分子量: 388.591
• InChiKey: ALFDMOBMDFGAMS-RJLPMABKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  28
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,7b,11,11,13a,13b-hexamethyl-1,2,2a1,6a,7,7a,7b,8,9,10,11,11a,12,13,13a, 13b-hexadecahydronaphtho[20,10:4,5]indeno[7,1-de][1,3]dioxepin-10-ol 在 臭氧 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 以80%的产率得到3-hydroxy-4,4,8,10,14-pentamethyl-17-oxohexadecahydro-1H-cyclopenta[a]phenanthren-12-yloxymethyl acetate
  参考文献：
  名称：

  Synthesis of selective 11 β -HSD1 inhibitors based on dammarane scaffold

  摘要：

  Inspired by natural 11 beta-HSD1 inhibitors hupehenols A - E, a ring-focused strategy was applied for the synthesis of 35 structurally diverse dammarane-type derivatives. These derivatives were effectively prepared from protopanaxadiol based on the modification of rings A and D. Among these compounds, ten were identified as selective 11 beta-HSD1 inhibitors (IC50 range: 101-1047 nM, SI range: 8-169) which exhibited inhibitory activities against human or mouse 11 beta-HSD1. Otherwise, we found 23a could selectively inhibit both human and mouse 11 beta-HSD1 with IC50 value of 994 and 213 nM (SI > 10 and > 47), respectively. Additionally, the molecular modelling results of 23a docking into the human and mouse 11 beta-HSD1 were in good agreement with the results from the enzyme inhibitory experiment. Moreover, valuable structural-activity relationship (SAR) information of dammarane-type 11 beta-HSD1 inhibitor was summarized. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.04.059
• 作为产物：
  描述：

  碘代三甲硅烷 、 1-[(3S,5R,8R,9R,10R,12R,13R,14R,17S)-3,12-bis(methoxymethoxy)-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone 在 六甲基二硅氮烷 、 四丁基氟化铵 作用下， 以 二氯甲烷 、 四氢呋喃 为溶剂， 反应 16.0h， 以81%的产率得到3,7b,11,11,13a,13b-hexamethyl-1,2,2a1,6a,7,7a,7b,8,9,10,11,11a,12,13,13a, 13b-hexadecahydronaphtho[20,10:4,5]indeno[7,1-de][1,3]dioxepin-10-ol
  参考文献：
  名称：

  Synthesis of selective 11 β -HSD1 inhibitors based on dammarane scaffold

  摘要：

  Inspired by natural 11 beta-HSD1 inhibitors hupehenols A - E, a ring-focused strategy was applied for the synthesis of 35 structurally diverse dammarane-type derivatives. These derivatives were effectively prepared from protopanaxadiol based on the modification of rings A and D. Among these compounds, ten were identified as selective 11 beta-HSD1 inhibitors (IC50 range: 101-1047 nM, SI range: 8-169) which exhibited inhibitory activities against human or mouse 11 beta-HSD1. Otherwise, we found 23a could selectively inhibit both human and mouse 11 beta-HSD1 with IC50 value of 994 and 213 nM (SI > 10 and > 47), respectively. Additionally, the molecular modelling results of 23a docking into the human and mouse 11 beta-HSD1 were in good agreement with the results from the enzyme inhibitory experiment. Moreover, valuable structural-activity relationship (SAR) information of dammarane-type 11 beta-HSD1 inhibitor was summarized. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.04.059