(1S,2S,3R,4S,5R,8R,9S,10R,13S)-4-acetoxy-2-benzoyloxy-5,20-epoxy-1-hydroxy-9,10-[(1S)-2,3-dihydroxypropylidenedioxy]tax-11-en-13-yl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-(2-pyridyl-N-oxide)propionate | 647840-10-6

• 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: (1S,2S,3R,4S,5R,8R,9S,10R,13S)-4-acetoxy-2-benzoyloxy-5,20-epoxy-1-hydroxy-9,10-[(1S)-2,3-dihydroxypropylidenedioxy]tax-11-en-13-yl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-(2-pyridyl-N-oxide)propionate
• CAS: 647840-10-6
• 化学式: C₄₅H₅₈N₂O₁₆
• 分子量: 882.959
• InChiKey: QMUPSPMMKGTGFQ-HFJFJENNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.46
• 重原子数：
  63.0
• 可旋转键数：
  10.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  252.78
• 氢给体数：
  5.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  (1S,2S,3R,4S,5R,8R,9S,10R,13S)-4-acetoxy-2-benzoyloxy-5,20-epoxy-1-hydroxy-9,10-[(1S)-2,3-dihydroxypropylidenedioxy]tax-11-en-13-yl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-(2-pyridyl-N-oxide)propionate 在 sodium periodate 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 为溶剂， 反应 0.67h， 生成 (1S,2S,3R,4S,5R,8R,9S,10R,13S)-4-acetoxy-2-benzoyloxy-5,20-epoxy-1-hydroxy-9,10-[(1S)-2-(morpholino)ethylidenedioxy]tax-11-en-13-yl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-(2-pyridyl-N-oxide)propionate
  参考文献：
  名称：

  New highly active taxoids from 9β-Dihydrobaccatin-9,10-acetals. Part 4

  摘要：

  It was shown that a new taxane analogue 3, which exhibited both in vitro antitumor activity and in vivo efficacy by both iv and po administration, was prone to be metabolized by human liver microsomes. We identified a major metabolite, M-1. generated by human liver microsomes as 20a, a hydroxylated compound at the pyridine ring of 3. To improve the metabolic stability of 3, we designed and synthesized new taxane analogues based on the structure of M-1. and obtained some compounds that maintained excellent antitumor activity and were scarcely metabolized by human liver microsomes. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00454-1
• 作为产物：
  描述：

  (1S,2S,3R,4S,5R,8R,9S,10R,13S)-4-(acetoxy)-2-(benzoyloxy)-5,20-epoxy-1-hyd roxy-9,10-[(1S)-2-propenylidenedioxy]tax-11-en-13-yl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-(2-pyridyl)propionate 在 四氧化锇 、 N-甲基吗啉氧化物 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 氯仿 、 水 、 丙酮 为溶剂， 反应 1.0h， 生成 (1S,2S,3R,4S,5R,8R,9S,10R,13S)-4-acetoxy-2-benzoyloxy-5,20-epoxy-1-hydroxy-9,10-[(1S)-2,3-dihydroxypropylidenedioxy]tax-11-en-13-yl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-(2-pyridyl-N-oxide)propionate
  参考文献：
  名称：

  New highly active taxoids from 9β-Dihydrobaccatin-9,10-acetals. Part 4

  摘要：

  It was shown that a new taxane analogue 3, which exhibited both in vitro antitumor activity and in vivo efficacy by both iv and po administration, was prone to be metabolized by human liver microsomes. We identified a major metabolite, M-1. generated by human liver microsomes as 20a, a hydroxylated compound at the pyridine ring of 3. To improve the metabolic stability of 3, we designed and synthesized new taxane analogues based on the structure of M-1. and obtained some compounds that maintained excellent antitumor activity and were scarcely metabolized by human liver microsomes. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00454-1