(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-(3-benzyloxy-2-pyridyl)-3-(tert-butoxycarbonylamino)-2-hydroxypropionate | 647840-35-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 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-(morpholino)ethylidenedioxy]tax-11-en-13-yl (2R,3S)-3-(3-benzyloxy-2-pyridyl)-3-(tert-butoxycarbonylamino)-2-hydroxypropionate
• CAS: 647840-35-5
• 化学式: C₅₅H₆₉N₃O₁₅
• 分子量: 1012.16
• InChiKey: ORCBPVJLBRHQLT-KIKOFXJMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.78
• 重原子数：
  73.0
• 可旋转键数：
  13.0
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  219.97
• 氢给体数：
  3.0
• 氢受体数：
  17.0

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-(morpholino)ethylidenedioxy]tax-11-en-13-yl (2R,3S)-3-(3-benzyloxy-2-pyridyl)-3-(tert-butoxycarbonylamino)-2-hydroxypropionate 在 palladium dihydroxide 氢气 作用下， 以 乙醇 为溶剂， 以84%的产率得到(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-(3-hydroxy-2-pyridyl)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：

  3-苄氧基-2-甲酰基吡啶 在 4-二甲氨基吡啶 、 sodium periodate 、 四氧化锇 、 四丁基氟化铵 、 sodium cyanoborohydride 、 溶剂黄146 、 N-甲基吗啉氧化物 、 lithium hexamethyldisilazane 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 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-(morpholino)ethylidenedioxy]tax-11-en-13-yl (2R,3S)-3-(3-benzyloxy-2-pyridyl)-3-(tert-butoxycarbonylamino)-2-hydroxypropionate
  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