3'-N-[β-D-galactopyranosyl-(1->4)-O-1-deoxy-D-glucit-1-yl]doxorubicin

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: 3'-N-[β-D-galactopyranosyl-(1->4)-O-1-deoxy-D-glucit-1-yl]doxorubicin
• 英文别名: (7S,9S)-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-7-[(2R,4S,5S,6S)-5-hydroxy-6-methyl-4-[[(2S,3R,4R,5R)-2,3,5,6-tetrahydroxy-4-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyhexyl]amino]oxan-2-yl]oxy-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione
• 化学式: C₃₉H₅₁NO₂₁
• 分子量: 869.828
• InChiKey: QKANNEODFFFYAD-QUKPEYAMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  61
• 可旋转键数：
  15
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  372
• 氢给体数：
  14
• 氢受体数：
  22

反应信息

• 作为产物：
  描述：

  在 氢溴酸 、 sodium formate 作用下， 以 甲醇 、 水 为溶剂， 生成 3'-N-[β-D-galactopyranosyl-(1->4)-O-1-deoxy-D-glucit-1-yl]doxorubicin
  参考文献：
  名称：

  Synthesis and antitumor activity of new d-galactose-containing derivatives of doxorubicin

  摘要：

  A general scheme of synthesis of antibiotic doxorubicin derivatives is based on the 13-dimethyl ketal of 14-bromodaunorubicin (4). The interaction of 4 with melibiose (5), lactose (6), 3-methoxy-4-O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-4-oxybenzaldehyde (12) or 4-O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-4-oxybenzaldehyde (13) by reductive alkylation followed by hydrolysis of the corresponding intermediate bromoketals produced 3'-N-[alpha-D-galactopyranosyl-(1-->6)-O-1-deoxy-D-glucit-1-yl]doxorubicin (7), 3'-N-[beta-D-galactopyranosyl-(1-->4)-O-1-deoxy-D-glucit-1-yl]doxorubicin (8), 3'-N-[3"-methoxy-4"-O-(beta-D-galactopyranosyl)-4"-oxybenzyl]doxorubicin (16), and 3'-N-[4"-O-(beta-D-galactopyranosyl)-4"-oxybenzyl]doxorubicin (17). Cytotoxic and antitumor activity of the synthesized drug candidates compared to the parent doxorubicin was studied using various experimental models, in particular, on mice bearing lymphocyte leukemia P-388 at single and multiple i.v. injection regimens. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0008-6215(03)00181-2

文献信息

• Synthesis and antitumor activity of new d-galactose-containing derivatives of doxorubicin
  作者：Eugenia N. Olsufyeva、Anna N. Tevyashova、Ivan D. Trestchalin、Maria N. Preobrazhenskaya、David Platt、Anatole Klyosov

  DOI：10.1016/s0008-6215(03)00181-2

  日期：2003.6

  A general scheme of synthesis of antibiotic doxorubicin derivatives is based on the 13-dimethyl ketal of 14-bromodaunorubicin (4). The interaction of 4 with melibiose (5), lactose (6), 3-methoxy-4-O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-4-oxybenzaldehyde (12) or 4-O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-4-oxybenzaldehyde (13) by reductive alkylation followed by hydrolysis of the corresponding intermediate bromoketals produced 3'-N-[alpha-D-galactopyranosyl-(1-->6)-O-1-deoxy-D-glucit-1-yl]doxorubicin (7), 3'-N-[beta-D-galactopyranosyl-(1-->4)-O-1-deoxy-D-glucit-1-yl]doxorubicin (8), 3'-N-[3"-methoxy-4"-O-(beta-D-galactopyranosyl)-4"-oxybenzyl]doxorubicin (16), and 3'-N-[4"-O-(beta-D-galactopyranosyl)-4"-oxybenzyl]doxorubicin (17). Cytotoxic and antitumor activity of the synthesized drug candidates compared to the parent doxorubicin was studied using various experimental models, in particular, on mice bearing lymphocyte leukemia P-388 at single and multiple i.v. injection regimens. (C) 2003 Elsevier Science Ltd. All rights reserved.