(9R)-7,8,9,10-tetrahydro-6,9,11-trihydroxy-4-methoxy-5,12-dioxonaphthacene-9-carboxylic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 并四苯
• 英文名称: (9R)-7,8,9,10-tetrahydro-6,9,11-trihydroxy-4-methoxy-5,12-dioxonaphthacene-9-carboxylic acid
• 英文别名: (2R)-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-3,4-dihydro-1H-tetracene-2-carboxylic acid
• 化学式: C₂₀H₁₆O₈
• 分子量: 384.342
• InChiKey: BDFZPQNYACBTLK-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  141
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (5Z)-1-thia-5-cyclodecene-3,8-diyn-7-ol 、 (9R)-7,8,9,10-tetrahydro-6,9,11-trihydroxy-4-methoxy-5,12-dioxonaphthacene-9-carboxylic acid 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以17%的产率得到(5Z)-7-<((9R)-7,8,9,10-tetrahydro-6,9,11-trihydroxy-4-methoxy-5,12-dioxonaphthacene-9-carbonyl)oxy>-1-thia-5-cyclodecene-3,8-diyne
  参考文献：
  名称：

  Molecular Design, Chemical Synthesis, and Study of Novel Enediyne-Sulfide Systems Related to the Neocarzinostatin Chromophore

  摘要：

  The design and synthesis of the novel monocyclic enediyne-sulfide systems and their chemical and DNA cleavage properties are described. The parent enediyne-sulfide 6 possessing a hydroxy group at the allylic position was effectively synthesized via the cross-coupling of the cis-vinyl iodide 11 and the acetylene derivative 12 using a Pd(O)-Cu(I) catalyst and the cyclization reaction of the acyclic dibromide 20 employing sodium sulfide as the key steps. In addition, the esterifications of 6 using appropriate procedures provided a series of its simple derivatives 21-29 and the hybrids 38-44 containing naturally occurring intercalators, all of which are quite stable when handled at ambient temperature. The representative enediyne-sulfide 22 was smoothly aromatized by 1,8-diazabicyclo[5.4.0]undec-7-ene in cyclohexa-1,4-diene through radical pathways and by a hydroxy anion in dimethyl sulfoxide-Tris-HCl, pH 8.5 buffer through a polar pathway. Furthermore, it was clearly found that all enediyne-sulfides cleaved DNA under alkaline conditions without any additive and the hybrids 38 and 44, each of which has the aromatic moiety of the neocarzinostatin chromophore and manzamins, respectively, exhibited the strongest DNA cleaving abilities with the identical high purine base (G > A) selectivity.

  DOI：

  10.1021/ja00122a012
• 作为产物：
  描述：

  6,9,11-三羟基-9-(2-羟基乙酰基)-4-甲氧基-8,10-二氢-7H-并四苯-5,12-二酮 在 过碘酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 以87%的产率得到(9R)-7,8,9,10-tetrahydro-6,9,11-trihydroxy-4-methoxy-5,12-dioxonaphthacene-9-carboxylic acid
  参考文献：
  名称：

  Molecular Design, Chemical Synthesis, and Study of Novel Enediyne-Sulfide Systems Related to the Neocarzinostatin Chromophore

  摘要：

  The design and synthesis of the novel monocyclic enediyne-sulfide systems and their chemical and DNA cleavage properties are described. The parent enediyne-sulfide 6 possessing a hydroxy group at the allylic position was effectively synthesized via the cross-coupling of the cis-vinyl iodide 11 and the acetylene derivative 12 using a Pd(O)-Cu(I) catalyst and the cyclization reaction of the acyclic dibromide 20 employing sodium sulfide as the key steps. In addition, the esterifications of 6 using appropriate procedures provided a series of its simple derivatives 21-29 and the hybrids 38-44 containing naturally occurring intercalators, all of which are quite stable when handled at ambient temperature. The representative enediyne-sulfide 22 was smoothly aromatized by 1,8-diazabicyclo[5.4.0]undec-7-ene in cyclohexa-1,4-diene through radical pathways and by a hydroxy anion in dimethyl sulfoxide-Tris-HCl, pH 8.5 buffer through a polar pathway. Furthermore, it was clearly found that all enediyne-sulfides cleaved DNA under alkaline conditions without any additive and the hybrids 38 and 44, each of which has the aromatic moiety of the neocarzinostatin chromophore and manzamins, respectively, exhibited the strongest DNA cleaving abilities with the identical high purine base (G > A) selectivity.

  DOI：

  10.1021/ja00122a012

文献信息

• [EN] ANTHRACYCLINE DERIVATIVE CONJUGATES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS ANTITUMOR COMPOUNDS<br/>[FR] CONJUGUÉS DE DÉRIVÉS D'ANTHRACYCLINE, PROCÉDÉ DE PRÉPARATION ASSOCIÉ ET UTILISATION COMME COMPOSÉS ANTITUMORAUX
  申请人：GENENTECH INC

  公开号：WO2010009124A2

  公开（公告）日：2010-01-21

  The present invention relates to conjugates of therapeutically useful anthracyclines with carriers such as polyclonal and monoclonal antibodies, proteins or peptides of natural or synthetic origin; methods for their preparation, pharmaceutical composition containing them and use thereof in treating certain mammalian tumors.
• Molecular Design, Chemical Synthesis, and Study of Novel Enediyne-Sulfide Systems Related to the Neocarzinostatin Chromophore
  作者：Kazunobu Toshima、Kazumi Ohta、Aya Ohashi、Takatsugu Nakamura、Masaya Nakata、Kuniaki Tatsuta、Shuichi Matsumura

  DOI：10.1021/ja00122a012

  日期：1995.5

  The design and synthesis of the novel monocyclic enediyne-sulfide systems and their chemical and DNA cleavage properties are described. The parent enediyne-sulfide 6 possessing a hydroxy group at the allylic position was effectively synthesized via the cross-coupling of the cis-vinyl iodide 11 and the acetylene derivative 12 using a Pd(O)-Cu(I) catalyst and the cyclization reaction of the acyclic dibromide 20 employing sodium sulfide as the key steps. In addition, the esterifications of 6 using appropriate procedures provided a series of its simple derivatives 21-29 and the hybrids 38-44 containing naturally occurring intercalators, all of which are quite stable when handled at ambient temperature. The representative enediyne-sulfide 22 was smoothly aromatized by 1,8-diazabicyclo[5.4.0]undec-7-ene in cyclohexa-1,4-diene through radical pathways and by a hydroxy anion in dimethyl sulfoxide-Tris-HCl, pH 8.5 buffer through a polar pathway. Furthermore, it was clearly found that all enediyne-sulfides cleaved DNA under alkaline conditions without any additive and the hybrids 38 and 44, each of which has the aromatic moiety of the neocarzinostatin chromophore and manzamins, respectively, exhibited the strongest DNA cleaving abilities with the identical high purine base (G > A) selectivity.