(1'R,4'R,8'S)-4'-acetyl-8'-(dimethoxymethyl)-9',10'-dimethylidene-11'-oxatricyclo<6.2.1.0^2',7'>undec-2'(7')-en-4'-yl (1R,5S,7R)-3-ethyl-2-oxo-6,8-dioxa-3-azabicyclo<3.2.1>octane-7-exo-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧氮杂卓类
• 英文名称: (1'R,4'R,8'S)-4'-acetyl-8'-(dimethoxymethyl)-9',10'-dimethylidene-11'-oxatricyclo<6.2.1.0^2',7'>undec-2'(7')-en-4'-yl (1R,5S,7R)-3-ethyl-2-oxo-6,8-dioxa-3-azabicyclo<3.2.1>octane-7-exo-carboxylate
• 英文别名: [(1R,4R,8S)-4-acetyl-8-(dimethoxymethyl)-9,10-dimethylidene-11-oxatricyclo[6.2.1.02,7]undec-2(7)-en-4-yl] (1R,5S,7R)-3-ethyl-2-oxo-6,8-dioxa-3-azabicyclo[3.2.1]octane-7-carboxylate
• 化学式: C₂₅H₃₁NO₉
• 分子量: 489.522
• InChiKey: QAQDNMHPGNYABC-GKNAGVKSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-硝基苯硫氯 、 (1'R,4'R,8'S)-4'-acetyl-8'-(dimethoxymethyl)-9',10'-dimethylidene-11'-oxatricyclo<6.2.1.0^2',7'>undec-2'(7')-en-4'-yl (1R,5S,7R)-3-ethyl-2-oxo-6,8-dioxa-3-azabicyclo<3.2.1>octane-7-exo-carboxylate 以 溶剂黄146 为溶剂， 反应 6.0h， 以12%的产率得到(1'R,4'S,8'S)-4'-acetyl-10'-(chloromethyl)-8'-(dimethoxymethyl)-9'-methylidene-10'-(2''-nitrophenylthio)-11'-oxatricyclo<6.2.1.0^2,7>undec-2'(7')-en-4'-yl (1R,5S,7R)-3-ethyl-2-oxo-6,8-dioxa-3-azabicyclo(3.2.1)octane-7-exo-carboxylate
  参考文献：
  名称：

  远程取代基对1，3-二烯的亲电加成有影响。（2R）-5-（乙酰氧基甲基）-2-乙酰基1,2,3,4-四氢-10-甲氧基萘并-2,12-二乙酸二乙酯的合成

  摘要：

  向1-（二甲氧基甲基）-2,3,5,6-四亚甲基-7-氧杂双环[2.2.1]庚烷（4）中添加一当量的2-硝基苯亚磺酰氯是高度区域选择性的，得到2-（氯甲基）-1 -（二甲氧基甲基）-5，6-二甲基-3-[（2-硝基苯硫基）甲基] -7-氧杂双环[2.2.1]庚-2-烯（9）。2-硝基苯-亚磺酰氯与8-（二甲氧基甲基）-9,10-二甲叉基-11-氧三环的反应[6.2.1.0 2,7] undec-2（7）-en-4-yl甲基酮衍生物（5，（-）-6）也具有区域选择性，可得到1,2-取代的混合物，而不是竞争性马尔可夫尼可夫和反马尔可夫尼可夫产生的1,4-加合物在加成方式中，距离8-二甲氧基甲基取代基最远的烯烃部分是优选的。这些加合物经历了碱诱导的消除反应，形成了环硫基和氯取代的二烯，这些环加到2,3-二氢苯并茴香醚中，从而生成了由高度“邻位”区域选择性Diels-Alder添加得到的产物。无论

  DOI：

  10.1016/0040-4020(95)00317-2
• 作为产物：
  描述：

  1-(dimethoxymethyl)-2,3,5,6-tetramethylidene-7-oxabicyclo<2.2.1>heptane 、 1-acetylvinyl (1S,5R,7S)-3-ethyl-2-oxo-6,8-dioxa-3-azabicyclo<3.2.1>octane-7-exo-carboxylate 在 三氟化硼乙醚 作用下， 生成 (1'R,4'R,8'S)-4'-acetyl-8'-(dimethoxymethyl)-9',10'-dimethylidene-11'-oxatricyclo<6.2.1.0^2',7'>undec-2'(7')-en-4'-yl (1R,5S,7R)-3-ethyl-2-oxo-6,8-dioxa-3-azabicyclo<3.2.1>octane-7-exo-carboxylate 、 (1R,5S,7R)-3-Ethyl-2-oxo-6,8-dioxa-3-aza-bicyclo[3.2.1]octane-7-carboxylic acid (1S,4S,8R)-4-acetyl-8-dimethoxymethyl-9,10-dimethylene-11-oxa-tricyclo[6.2.1.0^2,7]undec-2⁽⁷⁾-en-4-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

文献信息

• Remote substituent effect on the electrophilic additions of 1,3-dienes. Synthesis of (2R)-5-(acetoxymethyl)-2-acetyl-1,2,3,4-tetrahydro-10-methoxynaphthacene-2,12-diyl diacetate
  作者：Hervé Mosimann、Zoltán Dienes、Pierre Vogel

  DOI：10.1016/0040-4020(95)00317-2

  日期：1995.6

  5,6-tetramethylidene-7-oxabicyclo[2.2.1]heptane (4) is highly regioselective giving 2-(chloromethyl)-1-(dimethoxymethyl)-5,6-dimethylidene-3-[(2-nitrophenylthio)methyl]-7-oxabicyclo[2.2.1]hept-2-ene (9). The reaction of 2-nitrobenzene-sulfenyl chloride with 8-(dimethoxymethyl)-9,10-dimethylidene-11-oxatricyclo[6.2.1.02,7]undec-2(7)-en-4-yl methyl ketone derivatives (5, (-)-6) was also regioselective

  向1-（二甲氧基甲基）-2,3,5,6-四亚甲基-7-氧杂双环[2.2.1]庚烷（4）中添加一当量的2-硝基苯亚磺酰氯是高度区域选择性的，得到2-（氯甲基）-1 -（二甲氧基甲基）-5，6-二甲基-3-[（2-硝基苯硫基）甲基] -7-氧杂双环[2.2.1]庚-2-烯（9）。2-硝基苯-亚磺酰氯与8-（二甲氧基甲基）-9,10-二甲叉基-11-氧三环的反应[6.2.1.0 2,7] undec-2（7）-en-4-yl甲基酮衍生物（5，（-）-6）也具有区域选择性，可得到1,2-取代的混合物，而不是竞争性马尔可夫尼可夫和反马尔可夫尼可夫产生的1,4-加合物在加成方式中，距离8-二甲氧基甲基取代基最远的烯烃部分是优选的。这些加合物经历了碱诱导的消除反应，形成了环硫基和氯取代的二烯，这些环加到2,3-二氢苯并茴香醚中，从而生成了由高度“邻位”区域选择性Diels-Alder添加得到的产物。无论
• Asymmetric Synthesis and DNA Intercalation of (−)-6-[[(Aminoalkyl)oxy]methyl]-4-demethoxy-6,7- dideoxydaunomycinones¹^,
  作者：Zoltán Dienes、Pierre Vogel

  DOI：10.1021/jo960606z

  日期：1996.1.1

  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.