(1R,5S,7R)-3-Ethyl-2-oxo-6,8-dioxa-3-aza-bicyclo[3.2.1]octane-7-carboxylic acid (R)-12-acetoxy-2-acetyl-5-{3-[allyloxycarbonyl-(3-allyloxycarbonylamino-propyl)-amino]-propoxymethyl}-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-2-yl ester | 181943-83-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 并四苯
• 英文名称: (1R,5S,7R)-3-Ethyl-2-oxo-6,8-dioxa-3-aza-bicyclo[3.2.1]octane-7-carboxylic acid (R)-12-acetoxy-2-acetyl-5-{3-[allyloxycarbonyl-(3-allyloxycarbonylamino-propyl)-amino]-propoxymethyl}-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-2-yl ester
• 英文别名: [(2R)-2-acetyl-12-acetyloxy-6,11-dioxo-5-[3-[prop-2-enoxycarbonyl-[3-(prop-2-enoxycarbonylamino)propyl]amino]propoxymethyl]-3,4-dihydro-1H-tetracen-2-yl] (1R,5S,7R)-3-ethyl-2-oxo-6,8-dioxa-3-azabicyclo[3.2.1]octane-7-carboxylate
• CAS: 181943-83-9
• 化学式: C₄₅H₅₁N₃O₁₅
• 分子量: 873.911
• InChiKey: ONXAAILYXDLBAA-TZFPYUKJSA-N

物化性质

• 沸点：
  983.714±65.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.380±0.10 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  63
• 可旋转键数：
  23
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  220
• 氢给体数：
  1
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  (1R,5S,7R)-3-Ethyl-2-oxo-6,8-dioxa-3-aza-bicyclo[3.2.1]octane-7-carboxylic acid (R)-12-acetoxy-2-acetyl-5-{3-[allyloxycarbonyl-(3-allyloxycarbonylamino-propyl)-amino]-propoxymethyl}-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-2-yl ester 在 lithium hydroxide 、 bis(triphenylphosphine) palladium (Il) acetate 、 水 、 三正丁基氢锡 作用下， 生成 (R)-8-Acetyl-11-[3-(3-amino-propylamino)-propoxymethyl]-6,8-dihydroxy-7,8,9,10-tetrahydro-naphthacene-5,12-dione
  参考文献：
  名称：

  Asymmetric Synthesis and DNA Intercalation of (−)-6-[[(Aminoalkyl)oxy]methyl]-4-demethoxy-6,7- dideoxydaunomycinones^1,

  摘要：

  The BP3 . Et(2)O-promoted Diels-Alder addition of 1-acetylvinyl RADO(Et)-ate (RADO(Et)-ate = 3-ethyl-2-oxo-6,8-dioxa-3-azabicylo[3.2.1]octane-7-exo-carboxylate) to 1-(dimethosymethyl)-2,3,5,6-tetramethylidene-7-oxabicyclo[2.2.1]heptane led to one major monoadduct that added to 1,2-didehydrobenzene and was converted into (-)-4-demethoxy-7-deoxydaunomycinone and (2R)-12-acetoxy-2-acetyl-5-(bromomethyl)-1,2,3,4-tetrahydronaphthacen-2-yl RADO(Et)-ate. The latter compound was used to construct (8R)-8-acetyl-6,8-dihydroxy-11-[[(3'-[(aminopropyl)oxy]-, -4'-[(aminobutyl)oxy], and -5'-[(aminopenty)oxy]methyl]-7,8,9,10-tetrahydronaphthacene-5,12-dione hydrochloride (-)-8, (-)-9, (-)-10, respectively, as well as (8R)-8-acetyl-6,8-dihydroxy-11-[[[2'-[(3 ''-aminopropyl)amino]ethyl]oxy]-((-)-11) and -[[[3'-[(3 ''-aminopropyl)amino]propyl]oxy]methyl]7,8,9,10--tetrahydronaphthacene-5,12-dione hydrochloride ((-)-12). (8R)-8-Acetyl-6,8-dihydroxy-11-[[(alpha-L-diaunosaminyl)oxy]methyl]-7,8,9,10-tetrahydronaphthacene-5,12-dione hydrachloride ((-)-13), a mimic of idarubicin, was also prepared. Absorbance and fluorescence titration experiments showed (-)-8, (-)-9, and (-)-10 to intercalate calf thymus DNA whereas (-)-11, (-)-12, and (-)-13 did not. The best intercalator was (-)-9 (K-b = (1.1 +/- 0.1) x 10(5) M(-1)) with the [(4'-aminobutyl)oxy]-methyl chain. Inhibition of topoisomerase II-induced DNA strand religation wats observed for (-)-8 at a concentration of 50 mu M.

  DOI：

  10.1021/jo960606z
• 作为产物：
  描述：

  [(2R)-2-acetyl-12-acetyloxy-5-(bromomethyl)-3,4-dihydro-1H-tetracen-2-yl] (1R,5S,7R)-3-ethyl-2-oxo-6,8-dioxa-3-azabicyclo[3.2.1]octane-7-carboxylate 在 chromium(VI) oxide 、 4 A molecular sieve 、 硫酸 、 silver trifluoromethanesulfonate 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 0.08h， 生成 (1R,5S,7R)-3-Ethyl-2-oxo-6,8-dioxa-3-aza-bicyclo[3.2.1]octane-7-carboxylic acid (R)-12-acetoxy-2-acetyl-5-{3-[allyloxycarbonyl-(3-allyloxycarbonylamino-propyl)-amino]-propoxymethyl}-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-2-yl ester
  参考文献：
  名称：

  Asymmetric Synthesis and DNA Intercalation of (−)-6-[[(Aminoalkyl)oxy]methyl]-4-demethoxy-6,7- dideoxydaunomycinones^1,

  摘要：

  The BP3 . Et(2)O-promoted Diels-Alder addition of 1-acetylvinyl RADO(Et)-ate (RADO(Et)-ate = 3-ethyl-2-oxo-6,8-dioxa-3-azabicylo[3.2.1]octane-7-exo-carboxylate) to 1-(dimethosymethyl)-2,3,5,6-tetramethylidene-7-oxabicyclo[2.2.1]heptane led to one major monoadduct that added to 1,2-didehydrobenzene and was converted into (-)-4-demethoxy-7-deoxydaunomycinone and (2R)-12-acetoxy-2-acetyl-5-(bromomethyl)-1,2,3,4-tetrahydronaphthacen-2-yl RADO(Et)-ate. The latter compound was used to construct (8R)-8-acetyl-6,8-dihydroxy-11-[[(3'-[(aminopropyl)oxy]-, -4'-[(aminobutyl)oxy], and -5'-[(aminopenty)oxy]methyl]-7,8,9,10-tetrahydronaphthacene-5,12-dione hydrochloride (-)-8, (-)-9, (-)-10, respectively, as well as (8R)-8-acetyl-6,8-dihydroxy-11-[[[2'-[(3 ''-aminopropyl)amino]ethyl]oxy]-((-)-11) and -[[[3'-[(3 ''-aminopropyl)amino]propyl]oxy]methyl]7,8,9,10--tetrahydronaphthacene-5,12-dione hydrochloride ((-)-12). (8R)-8-Acetyl-6,8-dihydroxy-11-[[(alpha-L-diaunosaminyl)oxy]methyl]-7,8,9,10-tetrahydronaphthacene-5,12-dione hydrachloride ((-)-13), a mimic of idarubicin, was also prepared. Absorbance and fluorescence titration experiments showed (-)-8, (-)-9, and (-)-10 to intercalate calf thymus DNA whereas (-)-11, (-)-12, and (-)-13 did not. The best intercalator was (-)-9 (K-b = (1.1 +/- 0.1) x 10(5) M(-1)) with the [(4'-aminobutyl)oxy]-methyl chain. Inhibition of topoisomerase II-induced DNA strand religation wats observed for (-)-8 at a concentration of 50 mu M.

  DOI：

  10.1021/jo960606z