8-acetyl-10-<(3-amino-2,3,6-trideoxy-α-lyxo-hexopyranosyl)oxy>-1-methoxy-7,9,10,12-tetrahydro-6,8,11-trihydroxy-5(8H)-naphthacenone | 148876-08-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 8-acetyl-10-<(3-amino-2,3,6-trideoxy-α-lyxo-hexopyranosyl)oxy>-1-methoxy-7,9,10,12-tetrahydro-6,8,11-trihydroxy-5(8H)-naphthacenone
• 英文别名: (8S,10S)-8-acetyl-10-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,8,11-trihydroxy-1-methoxy-7,9,10,12-tetrahydrotetracen-5-one
• CAS: 148876-08-8
• 化学式: C₂₇H₃₁NO₉
• 分子量: 513.544
• InChiKey: PTDWRWMVPNCSRF-KGXMSQJOSA-N

物化性质

• 沸点：
  746.2±60.0 °C(predicted)
• 密度：
  1.49±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  37
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  169
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  8-acetyl-10-<(3-amino-2,3,6-trideoxy-α-lyxo-hexopyranosyl)oxy>-1-methoxy-7,9,10,12-tetrahydro-6,8,11-trihydroxy-5(8H)-naphthacenone 在 氧气 、 三羟甲基氨基甲烷 作用下， 以 甲醇 为溶剂， 生成 2-acetyl-11-hydroxy-7-methoxy-5,12-naphthacenedione 、 5-deoxydaunorubicin
  参考文献：
  名称：

  Synthesis and redox chemistry of 5-deoxydaunomycin. A long-lived hydroquinone tautomer

  摘要：

  Reduction of 5-iminodaunomycin with dithionite in anaerobic methanol followed by lowering the pH to 3 and saturating with air led to deamination without glycosidic cleavage to yield 89% 5-deoxydaunomycin. An intermediate observed during the reaction is proposed to be the hydroquinone tautomer, 8-acetyl-12-amino-10-[(3-amino-2,3,6-trideoxy-alpha-lyxo-hexopyranosyl)oxy]-1-methoxy-7,9,10,12-tetrahydro-6,8,11-trihydroxy-5(8H)-naphthacenone hydrochloride (1), which loses ammonia with a half-life of 49 min. Anaerobic reduction of 5-deoxydaunomycin with bi(3,5,5-trimethyl-2-oxomorpholin-3-yl) (TM-3 dimer) in methanol buffered to an apparent pH of 8 yielded 26% recovered 5-deoxydaunomycin, 56% 5,7-dideoxydaunomycinone, and 18% 2-acetyl-11-hydroxy-7-methoxy-5,12-naphthacenedione (5) after 42 h and subsequent exposure to molecular oxygen. The reduction leads to relatively rapid formation of a long-lived transient proposed to be, 8-acetyl-10-[(3-amino-2,3,6-trideoxy-a-lyxo-hexopyranosyl)oxy]-l-methoxy-7,9,10,12-tetrahydro-6,8,11-trihydroxy-5(8H)-naphthacenone (4). Exposure of 4 at its maximum concentration to molecular oxygen yielded 88% recovered 5-deoxydaunomycin and 12% 5. Tetrahydronaphthacenone 4 disappeared with a half-life of 2283 min in the absence of oxygen and 16 min in air-saturated methanol. Mechanistic pathways to the products are proposed in Scheme II. Analysis of the apparent rate constants for disappearance of 4 indicates that 5-deoxydaunomycin undergoes glycosidic cleavage to its 7-deoxyaglycon 8000 times slower than daunomycin upon reduction to the hydroquinone state.

  DOI：

  10.1021/ja00066a012
• 作为产物：
  描述：

  柔红霉素 盐酸盐 在 platinum(IV) oxide 氢气 、 氯乙酸 作用下， 以 甲醇 为溶剂， 反应 0.33h， 生成 8-acetyl-10-<(3-amino-2,3,6-trideoxy-α-lyxo-hexopyranosyl)oxy>-1-methoxy-7,9,10,12-tetrahydro-6,8,11-trihydroxy-5(8H)-naphthacenone
  参考文献：
  名称：

  5-Deoxy, 12-Deoxy, 5,12-Bisdeoxy, and 4,5,12-Trisdeoxy Anthracyclines: Synthesis of New Analogues of Daunorubicin and Doxorubicin by Controlled Deoxygenation of the C-Ring.

  摘要：

  蒽喜啉类化合物多柔比星（1）和阿霉素（2）的氢化反应在位置5上发生选择性脱氧作用。对（1）和（2）的氢化还原反应产生了互补的位置控制，导致12-脱氧或5,12-双脱氧。这种化学反应可保留7-糖苷和侧链酮基团。它已经导致新的蒽喜啉类家族，具有母体化合物（1）和（2）的所有立体化学特性和大部分空间特性。这些家族的代表包括5-去氧（12），（15）；12-去氧（22），（23）；5,12-双去氧（34），（35）；以及4,5,12-三去氧系统（36）。所有这些都具有高抗癌活性。

  DOI：

  10.1071/ch99151

文献信息

• 5-Deoxy, 12-Deoxy, 5,12-Bisdeoxy, and 4,5,12-Trisdeoxy Anthracyclines: Synthesis of New Analogues of Daunorubicin and Doxorubicin by Controlled Deoxygenation of the C-Ring.
  作者：Donald W. Cameron、Geoffrey I. Feutrill、Peter G. Griffiths

  DOI：10.1071/ch99151

  日期：——

  Hydrogenation of the anthracyclines daunorubicin (1) and doxorubicin (2) gave selective deoxygenation at position 5. Hydride reduction of (1) and (2) gave complementary regiocontrol, leading to 12-deoxygenation or 5,12- bisdeoxygenation. This chemistry allows retention of the 7-glycoside and the side-chain carbonyl groups. It has led to new anthracycline families possessing all of the stereochemical and most of the spatial characteristics of the parent compounds (1) and (2). These are typified by 5-deoxy (12), (15); 12-deoxy (22), (23); 5,12-bisdeoxy (34), (35); and 4,5,12-trisdeoxy systems (36). All possess high anticancer activity.

  蒽喜啉类化合物多柔比星（1）和阿霉素（2）的氢化反应在位置5上发生选择性脱氧作用。对（1）和（2）的氢化还原反应产生了互补的位置控制，导致12-脱氧或5,12-双脱氧。这种化学反应可保留7-糖苷和侧链酮基团。它已经导致新的蒽喜啉类家族，具有母体化合物（1）和（2）的所有立体化学特性和大部分空间特性。这些家族的代表包括5-去氧（12），（15）；12-去氧（22），（23）；5,12-双去氧（34），（35）；以及4,5,12-三去氧系统（36）。所有这些都具有高抗癌活性。
• Synthesis and redox chemistry of 5-deoxydaunomycin. A long-lived hydroquinone tautomer
  作者：Barbara Ann Schweitzer、Tad H. Koch

  DOI：10.1021/ja00066a012

  日期：1993.6

  Reduction of 5-iminodaunomycin with dithionite in anaerobic methanol followed by lowering the pH to 3 and saturating with air led to deamination without glycosidic cleavage to yield 89% 5-deoxydaunomycin. An intermediate observed during the reaction is proposed to be the hydroquinone tautomer, 8-acetyl-12-amino-10-[(3-amino-2,3,6-trideoxy-alpha-lyxo-hexopyranosyl)oxy]-1-methoxy-7,9,10,12-tetrahydro-6,8,11-trihydroxy-5(8H)-naphthacenone hydrochloride (1), which loses ammonia with a half-life of 49 min. Anaerobic reduction of 5-deoxydaunomycin with bi(3,5,5-trimethyl-2-oxomorpholin-3-yl) (TM-3 dimer) in methanol buffered to an apparent pH of 8 yielded 26% recovered 5-deoxydaunomycin, 56% 5,7-dideoxydaunomycinone, and 18% 2-acetyl-11-hydroxy-7-methoxy-5,12-naphthacenedione (5) after 42 h and subsequent exposure to molecular oxygen. The reduction leads to relatively rapid formation of a long-lived transient proposed to be, 8-acetyl-10-[(3-amino-2,3,6-trideoxy-a-lyxo-hexopyranosyl)oxy]-l-methoxy-7,9,10,12-tetrahydro-6,8,11-trihydroxy-5(8H)-naphthacenone (4). Exposure of 4 at its maximum concentration to molecular oxygen yielded 88% recovered 5-deoxydaunomycin and 12% 5. Tetrahydronaphthacenone 4 disappeared with a half-life of 2283 min in the absence of oxygen and 16 min in air-saturated methanol. Mechanistic pathways to the products are proposed in Scheme II. Analysis of the apparent rate constants for disappearance of 4 indicates that 5-deoxydaunomycin undergoes glycosidic cleavage to its 7-deoxyaglycon 8000 times slower than daunomycin upon reduction to the hydroquinone state.