[(2R,3R,4S,5R,6R)-6-[4-[[[(4aR,5R,6aR,6aS,6bR,8aR,10S,12aR,14bS)-5,10-dihydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carbonyl]amino]methyl]triazol-1-yl]-4,5-diacetyloxy-3-[(2R,3R,4S,5R,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxyoxan-2-yl]methyl acetate | 1438765-24-2

• 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: [(2R,3R,4S,5R,6R)-6-[4-[[[(4aR,5R,6aR,6aS,6bR,8aR,10S,12aR,14bS)-5,10-dihydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carbonyl]amino]methyl]triazol-1-yl]-4,5-diacetyloxy-3-[(2R,3R,4S,5R,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxyoxan-2-yl]methyl acetate
• CAS: 1438765-24-2
• 化学式: C₅₉H₈₆N₄O₂₀
• 分子量: 1171.35
• InChiKey: WBSBCYXFCKKKEN-IHGQUDFDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  83
• 可旋转键数：
  22
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  312
• 氢给体数：
  3
• 氢受体数：
  22

反应信息

• 作为反应物：
  描述：

  [(2R,3R,4S,5R,6R)-6-[4-[[[(4aR,5R,6aR,6aS,6bR,8aR,10S,12aR,14bS)-5,10-dihydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carbonyl]amino]methyl]triazol-1-yl]-4,5-diacetyloxy-3-[(2R,3R,4S,5R,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxyoxan-2-yl]methyl acetate 在 甲醇 、 sodium methylate 作用下， 以86%的产率得到(4aR,5R,6aR,6aS,6bR,8aR,10S,12aR,14bS)-N-[[1-[(2R,3R,4R,5S,6R)-3,4-dihydroxy-6-(hydroxymethyl)-5-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]triazol-4-yl]methyl]-5,10-dihydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxamide
  参考文献：
  名称：

  Development of Oleanane-Type Triterpenes as a New Class of HCV Entry Inhibitors

  摘要：

  Development of hepatitis C virus (HCV) entry inhibitors represents an emerging approach that satisfies a tandem mechanism for use with other inhibitors in a multifaceted cocktail. By screening Chinese herbal extracts, oleanolic acid (OA) was found to display weak potency to inhibit HCV entry with an IC50 of 10 mu M. Chemical exploration of this triterpene compound revealed its pharmacophore requirement for blocking HCV entry, rings A, B, and E, are conserved while ring D is tolerant of some modifications. Hydroxylation at C-16 significantly enhanced its potency for inhibiting HCV entry with IC50 at 1.4 mu M. Further modification by conjugation of this new lead with a disaccharide at 28-COOH removed the undesired hemolytic effect and, more importantly, increased its potency by similar to 5-fold (54a, IC50 0.3 mu M). Formation of a triterpene dimer via a linker bearing triazole (70) dramatically increased its potency with IC50 at similar to 10 nM. Mechanistically, such functional triterpenes interrupt the interaction between HCV envelope protein E2 and its receptor CD81 via binding to E2, thus blocking virus and host cell recognition. This study establishes the importance of triterpene natural products as new leads for the development of potential HCV entry inhibitors.

  DOI：

  10.1021/jm301910a
• 作为产物：
  描述：

  刺囊酸 在 sodium carbonate 、 copper(II) sulfate 、 sodium ascorbate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.33h， 生成 [(2R,3R,4S,5R,6R)-6-[4-[[[(4aR,5R,6aR,6aS,6bR,8aR,10S,12aR,14bS)-5,10-dihydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carbonyl]amino]methyl]triazol-1-yl]-4,5-diacetyloxy-3-[(2R,3R,4S,5R,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxyoxan-2-yl]methyl acetate
  参考文献：
  名称：

  Development of Oleanane-Type Triterpenes as a New Class of HCV Entry Inhibitors

  摘要：

  Development of hepatitis C virus (HCV) entry inhibitors represents an emerging approach that satisfies a tandem mechanism for use with other inhibitors in a multifaceted cocktail. By screening Chinese herbal extracts, oleanolic acid (OA) was found to display weak potency to inhibit HCV entry with an IC50 of 10 mu M. Chemical exploration of this triterpene compound revealed its pharmacophore requirement for blocking HCV entry, rings A, B, and E, are conserved while ring D is tolerant of some modifications. Hydroxylation at C-16 significantly enhanced its potency for inhibiting HCV entry with IC50 at 1.4 mu M. Further modification by conjugation of this new lead with a disaccharide at 28-COOH removed the undesired hemolytic effect and, more importantly, increased its potency by similar to 5-fold (54a, IC50 0.3 mu M). Formation of a triterpene dimer via a linker bearing triazole (70) dramatically increased its potency with IC50 at similar to 10 nM. Mechanistically, such functional triterpenes interrupt the interaction between HCV envelope protein E2 and its receptor CD81 via binding to E2, thus blocking virus and host cell recognition. This study establishes the importance of triterpene natural products as new leads for the development of potential HCV entry inhibitors.

  DOI：

  10.1021/jm301910a

文献信息

• Development of Oleanane-Type Triterpenes as a New Class of HCV Entry Inhibitors
  作者：Fei Yu、Qi Wang、Zhen Zhang、Yiyun Peng、Yunyan Qiu、Yongying Shi、Yongxiang Zheng、Sulong Xiao、Han Wang、Xiaoxi Huang、Linyi Zhu、Kunbo Chen、Chuanke Zhao、Chuanling Zhang、Maorong Yu、Dian Sun、Lihe Zhang、Demin Zhou

  DOI：10.1021/jm301910a

  日期：2013.6.13

  Development of hepatitis C virus (HCV) entry inhibitors represents an emerging approach that satisfies a tandem mechanism for use with other inhibitors in a multifaceted cocktail. By screening Chinese herbal extracts, oleanolic acid (OA) was found to display weak potency to inhibit HCV entry with an IC50 of 10 mu M. Chemical exploration of this triterpene compound revealed its pharmacophore requirement for blocking HCV entry, rings A, B, and E, are conserved while ring D is tolerant of some modifications. Hydroxylation at C-16 significantly enhanced its potency for inhibiting HCV entry with IC50 at 1.4 mu M. Further modification by conjugation of this new lead with a disaccharide at 28-COOH removed the undesired hemolytic effect and, more importantly, increased its potency by similar to 5-fold (54a, IC50 0.3 mu M). Formation of a triterpene dimer via a linker bearing triazole (70) dramatically increased its potency with IC50 at similar to 10 nM. Mechanistically, such functional triterpenes interrupt the interaction between HCV envelope protein E2 and its receptor CD81 via binding to E2, thus blocking virus and host cell recognition. This study establishes the importance of triterpene natural products as new leads for the development of potential HCV entry inhibitors.