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