(1R)-1,2,3,4,6,11-六氢-4alpha-[[3-(甲基氨基)-2,3,6-三脱氧-alpha-L-来苏-己糖吡喃糖苷]氧基]-6,11-二氧代-2-乙基-2alpha,5,7-三羟基-1beta-萘并萘羧酸甲酯 | 67508-85-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 中文名称: (1R)-1,2,3,4,6,11-六氢-4alpha-[[3-(甲基氨基)-2,3,6-三脱氧-alpha-L-来苏-己糖吡喃糖苷]氧基]-6,11-二氧代-2-乙基-2alpha,5,7-三羟基-1beta-萘并萘羧酸甲酯
• 英文名称: 15-O-Methyl-D788-3
• 英文别名: 7-O-daunosaminylaklavinone；7-[α-L-daunosamino]-aklavinone；N,N-Didemethyl-1-deoxypyrromycin；methyl (1R,2R,4S)-4-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-2,5,7-trihydroxy-6,11-dioxo-3,4-dihydro-1H-tetracene-1-carboxylate
• CAS: 67508-85-4
• 化学式: C₂₈H₃₁NO₁₀
• 分子量: 541.555
• InChiKey: MCWLCHNOMBKWNJ-JXJKFGGBSA-N

物化性质

• 沸点：
  717.4±60.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  39
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  186
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (1R)-1,2,3,4,6,11-六氢-4alpha-[[3-(甲基氨基)-2,3,6-三脱氧-alpha-L-来苏-己糖吡喃糖苷]氧基]-6,11-二氧代-2-乙基-2alpha,5,7-三羟基-1beta-萘并萘羧酸甲酯 在 盐酸 作用下， 反应 0.5h， 生成 阿克拉菌酮
  参考文献：
  名称：

  New Anthracycline Antibiotics 10-epi-Oxaunomycin and 10-epi-11-Deoxyoxaunomycin.

  摘要：

  从蒽环类代谢物 D788-1（10-羧基-13-脱氧大环内酯霉素）和 D788-3（10-羧基-ll-脱氧-13-脱氧大环内酯霉素）光化学方法获得了两种新的蒽环类抗生素--10-表-氧杂霉素和 10-表-11-脱氧氧杂霉素，并考察了它们对培养的 LI210 白血病细胞的生长抑制活性。通过与奥沙霉素和 11-脱氧奥沙霉素进行比较，讨论了 C-10 的 S 构型和 C-11 的羟基对生物活性的影响。

  DOI：

  10.7164/antibiotics.48.1153
• 作为产物：
  描述：

  阿克拉菌酮 在 吡啶 、 四(三苯基膦)钯 、 1,3-二甲基巴比妥酸 、 三苯基膦氯金 、 pyridine hydrofluoride 、 双三氟甲烷磺酰亚胺银盐 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 (1R)-1,2,3,4,6,11-六氢-4alpha-[[3-(甲基氨基)-2,3,6-三脱氧-alpha-L-来苏-己糖吡喃糖苷]氧基]-6,11-二氧代-2-乙基-2alpha,5,7-三羟基-1beta-萘并萘羧酸甲酯
  参考文献：
  名称：

  Doxorubicin and Aclarubicin: Shuffling Anthracycline Glycans for Improved Anticancer Agents

  摘要：

  Anthracycline anticancer drugs doxorubicin and aclarubicin have been used in the clinic for several decades to treat various cancers. Although closely related structures, their molecular mode of action diverges, which is reflected in their biological activity profile. For a better understanding of the structure-function relationship of these drugs, we synthesized ten doxorubicin/aclarubicin hybrids varying in three distinct features: aglycon, glycan, and amine substitution pattern. We continued to evaluate their capacity to induce DNA breaks, histone eviction, and relocated topoisomerase II alpha in living cells. Furthermore, we assessed their cytotoxicity in various human tumor cell lines. Our findings underscore that histone eviction alone, rather than DNA breaks, contributes strongly to the overall cytotoxicity of anthracyclines, and structures containing N,N-dimethylamine at the reducing sugar prove that are more cytotoxic than their nonmethylated counterparts. This structural information will support further development of novel anthracycline variants with improved anticancer activity.

  DOI：

  10.1021/acs.jmedchem.0c01191

文献信息

• Doxorubicin and Aclarubicin: Shuffling Anthracycline Glycans for Improved Anticancer Agents
  作者：Dennis P. A. Wander、Sabina Y. van der Zanden、Gijsbert A. van der Marel、Herman S. Overkleeft、Jacques Neefjes、Jeroen D. C. Codée

  DOI：10.1021/acs.jmedchem.0c01191

  日期：2020.11.12

  Anthracycline anticancer drugs doxorubicin and aclarubicin have been used in the clinic for several decades to treat various cancers. Although closely related structures, their molecular mode of action diverges, which is reflected in their biological activity profile. For a better understanding of the structure-function relationship of these drugs, we synthesized ten doxorubicin/aclarubicin hybrids varying in three distinct features: aglycon, glycan, and amine substitution pattern. We continued to evaluate their capacity to induce DNA breaks, histone eviction, and relocated topoisomerase II alpha in living cells. Furthermore, we assessed their cytotoxicity in various human tumor cell lines. Our findings underscore that histone eviction alone, rather than DNA breaks, contributes strongly to the overall cytotoxicity of anthracyclines, and structures containing N,N-dimethylamine at the reducing sugar prove that are more cytotoxic than their nonmethylated counterparts. This structural information will support further development of novel anthracycline variants with improved anticancer activity.
• New Anthracycline Antibiotics 10-epi-Oxaunomycin and 10-epi-11-Deoxyoxaunomycin.
  作者：OSAMU JOHDO、H. NISHIDA、R. OKAMOTO、AKIHIRO YOSHIMOTO、TOMIO TAKEUCHI

  DOI：10.7164/antibiotics.48.1153

  日期：——

  Two new anthracycline antibiotics, 10-epi-oxaunomycin and 10-epi-11-deoxyoxaunomycin, were photochemically obtained from anthracycline metabolites D788-1 (10-carboxy-13-deoxocarminomycin) and D788-3 (10-carboxy-ll-deoxy-13-deoxocarminomycin) and were examined for their growth inhibitory activities on cultured LI210 leukemic cells. Effects of the S configuration of C-10 and a hydroxyl group at C-11 on the bioactivity are discussed in comparison with oxaunomycin and 11-deoxyoxaunomycin.

  从蒽环类代谢物 D788-1（10-羧基-13-脱氧大环内酯霉素）和 D788-3（10-羧基-ll-脱氧-13-脱氧大环内酯霉素）光化学方法获得了两种新的蒽环类抗生素--10-表-氧杂霉素和 10-表-11-脱氧氧杂霉素，并考察了它们对培养的 LI210 白血病细胞的生长抑制活性。通过与奥沙霉素和 11-脱氧奥沙霉素进行比较，讨论了 C-10 的 S 构型和 C-11 的羟基对生物活性的影响。