(7-Benzyloxy-1-methylene-1,2,3,4-tetrahydro-naphtho[2,1-b]azepin-5-yl)-(5,6,7-trimethoxy-1H-indol-2-yl)-methanone | 194221-96-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (7-Benzyloxy-1-methylene-1,2,3,4-tetrahydro-naphtho[2,1-b]azepin-5-yl)-(5,6,7-trimethoxy-1H-indol-2-yl)-methanone
• 英文别名: (1-methylidene-7-phenylmethoxy-3,4-dihydro-2H-benzo[g][1]benzazepin-5-yl)-(5,6,7-trimethoxy-1H-indol-2-yl)methanone
• CAS: 194221-96-0
• 化学式: C₃₄H₃₂N₂O₅
• 分子量: 548.638
• InChiKey: MGGCAUZVMAININ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  41
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  73
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (7-Benzyloxy-1-methylene-1,2,3,4-tetrahydro-naphtho[2,1-b]azepin-5-yl)-(5,6,7-trimethoxy-1H-indol-2-yl)-methanone 在 sodium hydroxide 、 dimethyl sulfide borane 、 双氧水 作用下， 生成 (7-Benzyloxy-1-hydroxymethyl-1,2,3,4-tetrahydro-naphtho[2,1-b]azepin-5-yl)-(5,6,7-trimethoxy-1H-indol-2-yl)-methanone
  参考文献：
  名称：

  Synthesis and Evaluation of CC-1065 and Duocarmycin Analogs Incorporating the 1,2,3,4,11,11a-Hexahydrocyclopropa[c]naphtho[2,1-b]azepin-6-one (CNA) Alkylation Subunit:  Structural Features that Govern Reactivity and Reaction Regioselectivity

  摘要：

  The synthesis of 1,2,3,4,11,11a-hexahydrocyclopropa[c]naphtho[2,1-b]azepin-6-one (CNA), a seven-membered C-ring analog of the alkylation subunits of CC-1065 and the duocarmycins, is detailed. The core structure of CNA was prepared through the implementation of an intramolecular Heck reaction for assemblage of the key tricyclic tetrahydronaphtho[2,1-b]azepine skeleton and a final Winstein Ar-3' spirocyclization for introduction of the reactive cyclopropane. A study of the solvolysis reactivity of N-BOC-CNA revealed that incorporation of the seven-membered fused C-ring system increased the reactivity 4750x compared to the corresponding five-membered C-ring analog. Solvolysis occurs with S(N)2 nucleophilic attack at the more substituted carbon of the activated cyclopropane to afford exclusively the abnormal ring expansion product in a reaction that was shown : to proceed with complete inversion of configuration at the reaction center. Single crystal X-ray structure analyses of N-CO2Me-CNA (29) and CNA (11) and their comparisons with X-ray structures of the corresponding five-and six-membered C-ring analogs revealed the structural origins of the solvolysis regioselectivity and reactivity. The regioselectivity may be attributed to the stereoelectronic alignment of the two available cyclopropane bonds with the cyclohexadienone pi-system which for 29 resides with the bond that extends to the more substituted cyclopropyl carbon. The increased reactivity may be due in part to the geometric alignment of the cyclopropane but more significantly is linked to a twist in the N-2 amide. X-ray analysis provides documentation of the disruption in the vinylogous amide stabilization as measured by a lengthening of the diagnostic C-N bond that accompanies the twist in the chi(1) dihedral angle of the N-2 amide. As the cross-conjugated vinylogous amide stabilization is diminished, the cyclopropane conjugation, bond lengths, and resulting reactivity increase. The unusual stability of the five-membered C-ring bearing alkylation subunits characteristic of the natural products is intimately linked to the extent of this vinylogous amide conjugation, and the studies support the proposal that catalysis for the DNA alkylation reaction may be due to a DNA binding-induced conformational change in the agents which serves to twist the linking N-2 amide, disrupting the vinylogous amide stabilization, and activating the agents for S(N)2 nucleophilic attack.

  DOI：

  10.1021/jo9707085
• 作为产物：
  描述：

  4-pentenyl mesylate 在 四(三苯基膦)钯 盐酸 、 sodium hydroxide 、 苄基三丁基氯化铵 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 、 苯 为溶剂， 反应 21.17h， 生成 (7-Benzyloxy-1-methylene-1,2,3,4-tetrahydro-naphtho[2,1-b]azepin-5-yl)-(5,6,7-trimethoxy-1H-indol-2-yl)-methanone
  参考文献：
  名称：

  Synthesis and Evaluation of CC-1065 and Duocarmycin Analogs Incorporating the 1,2,3,4,11,11a-Hexahydrocyclopropa[c]naphtho[2,1-b]azepin-6-one (CNA) Alkylation Subunit:  Structural Features that Govern Reactivity and Reaction Regioselectivity

  摘要：

  The synthesis of 1,2,3,4,11,11a-hexahydrocyclopropa[c]naphtho[2,1-b]azepin-6-one (CNA), a seven-membered C-ring analog of the alkylation subunits of CC-1065 and the duocarmycins, is detailed. The core structure of CNA was prepared through the implementation of an intramolecular Heck reaction for assemblage of the key tricyclic tetrahydronaphtho[2,1-b]azepine skeleton and a final Winstein Ar-3' spirocyclization for introduction of the reactive cyclopropane. A study of the solvolysis reactivity of N-BOC-CNA revealed that incorporation of the seven-membered fused C-ring system increased the reactivity 4750x compared to the corresponding five-membered C-ring analog. Solvolysis occurs with S(N)2 nucleophilic attack at the more substituted carbon of the activated cyclopropane to afford exclusively the abnormal ring expansion product in a reaction that was shown : to proceed with complete inversion of configuration at the reaction center. Single crystal X-ray structure analyses of N-CO2Me-CNA (29) and CNA (11) and their comparisons with X-ray structures of the corresponding five-and six-membered C-ring analogs revealed the structural origins of the solvolysis regioselectivity and reactivity. The regioselectivity may be attributed to the stereoelectronic alignment of the two available cyclopropane bonds with the cyclohexadienone pi-system which for 29 resides with the bond that extends to the more substituted cyclopropyl carbon. The increased reactivity may be due in part to the geometric alignment of the cyclopropane but more significantly is linked to a twist in the N-2 amide. X-ray analysis provides documentation of the disruption in the vinylogous amide stabilization as measured by a lengthening of the diagnostic C-N bond that accompanies the twist in the chi(1) dihedral angle of the N-2 amide. As the cross-conjugated vinylogous amide stabilization is diminished, the cyclopropane conjugation, bond lengths, and resulting reactivity increase. The unusual stability of the five-membered C-ring bearing alkylation subunits characteristic of the natural products is intimately linked to the extent of this vinylogous amide conjugation, and the studies support the proposal that catalysis for the DNA alkylation reaction may be due to a DNA binding-induced conformational change in the agents which serves to twist the linking N-2 amide, disrupting the vinylogous amide stabilization, and activating the agents for S(N)2 nucleophilic attack.

  DOI：

  10.1021/jo9707085

文献信息

• Synthesis and Evaluation of CC-1065 and Duocarmycin Analogs Incorporating the 1,2,3,4,11,11a-Hexahydrocyclopropa[<i>c</i>]naphtho[2,1-<i>b</i>]azepin-6-one (CNA) Alkylation Subunit:  Structural Features that Govern Reactivity and Reaction Regioselectivity
  作者：Dale L. Boger、Philip Turnbull

  DOI：10.1021/jo9707085

  日期：1997.8.1

  The synthesis of 1,2,3,4,11,11a-hexahydrocyclopropa[c]naphtho[2,1-b]azepin-6-one (CNA), a seven-membered C-ring analog of the alkylation subunits of CC-1065 and the duocarmycins, is detailed. The core structure of CNA was prepared through the implementation of an intramolecular Heck reaction for assemblage of the key tricyclic tetrahydronaphtho[2,1-b]azepine skeleton and a final Winstein Ar-3' spirocyclization for introduction of the reactive cyclopropane. A study of the solvolysis reactivity of N-BOC-CNA revealed that incorporation of the seven-membered fused C-ring system increased the reactivity 4750x compared to the corresponding five-membered C-ring analog. Solvolysis occurs with S(N)2 nucleophilic attack at the more substituted carbon of the activated cyclopropane to afford exclusively the abnormal ring expansion product in a reaction that was shown : to proceed with complete inversion of configuration at the reaction center. Single crystal X-ray structure analyses of N-CO2Me-CNA (29) and CNA (11) and their comparisons with X-ray structures of the corresponding five-and six-membered C-ring analogs revealed the structural origins of the solvolysis regioselectivity and reactivity. The regioselectivity may be attributed to the stereoelectronic alignment of the two available cyclopropane bonds with the cyclohexadienone pi-system which for 29 resides with the bond that extends to the more substituted cyclopropyl carbon. The increased reactivity may be due in part to the geometric alignment of the cyclopropane but more significantly is linked to a twist in the N-2 amide. X-ray analysis provides documentation of the disruption in the vinylogous amide stabilization as measured by a lengthening of the diagnostic C-N bond that accompanies the twist in the chi(1) dihedral angle of the N-2 amide. As the cross-conjugated vinylogous amide stabilization is diminished, the cyclopropane conjugation, bond lengths, and resulting reactivity increase. The unusual stability of the five-membered C-ring bearing alkylation subunits characteristic of the natural products is intimately linked to the extent of this vinylogous amide conjugation, and the studies support the proposal that catalysis for the DNA alkylation reaction may be due to a DNA binding-induced conformational change in the agents which serves to twist the linking N-2 amide, disrupting the vinylogous amide stabilization, and activating the agents for S(N)2 nucleophilic attack.