7-N-(2-anilinoethyl)mitomycin C

• 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-N-(2-anilinoethyl)mitomycin C
• 英文别名: [(4S,6S,7R,8S)-11-(2-anilinoethylamino)-7-methoxy-12-methyl-10,13-dioxo-2,5-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),11-dien-8-yl]methyl carbamate
• 化学式: C₂₃H₂₇N₅O₅
• 分子量: 453.498
• InChiKey: QGBAUSPUQGGPRS-USYHLRJESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  145
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  7-N-(2-anilinoethyl)mitomycin C 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 120.0h， 生成 Carbamic acid (1R,2S)-2-amino-1-methoxy-6-methyl-5,8-dioxo-7-(2-phenylamino-ethylamino)-2,3,5,8-tetrahydro-1H-pyrrolo[1,2-a]indol-9-ylmethyl ester 、 Carbamic acid (1S,2S)-2-amino-1-methoxy-6-methyl-5,8-dioxo-7-(2-phenylamino-ethylamino)-2,3,5,8-tetrahydro-1H-pyrrolo[1,2-a]indol-9-ylmethyl ester
  参考文献：
  名称：

  C(7)-Substituted Diaminomitomycins:  Synthesis, Structure, and Chemical Reactivity

  摘要：

  Five mitomycins (23-27) were prepared to determine if an appended C(7) diamine substituent would promote C(1) nucleophilic substitution transformations by covalent modification of the C(8) quinone group. The appended C(7) diamine units varied in the basicity of the terminal amine and in the type and length of the carbon backbone. The mitomycins were prepared in high yield by treatment of mitomycin A (28) with selected diamines. Mitomycin 25, which contained a C(7) 3-amino-2,2-dimethylpropylamine unit, underwent rapid conversion to the corresponding albomitomycin-type adduct 34 in which the C(8) quinone group was converted to the corresponding C(8) imine. Dissolution of each mitomycin (23, 24, 26, 27, and 34) in methanol (''pH'' 5.5, 25 degrees C) led to the production of the cis- and trans-C(1) methoxymitosenes. The rates of salvolysis were monitored by HPLC and followed pseudo-first-order kinetics. Modest rate enhancements (5.1-15.2-fold), compared with mitomycin C(1), were observed for 7-N-(2-aminobenzyl)mitomycin C (23) and 7-N(2-anilinoethyl)mitomycin C(24), the two mitomycins containing terminal aniline groups. Solvolysis of 23 gave the C(1) methoxymitosenes 37 and 38, in which the C(8) site was converted to the cyclized C(8) imine; solvolysis of 24 gave C(1) methoxy products 39 and 40, in which the C(8) quinone unit was not modified. No appreciable rate enhancements over 1 were observed for 26 and 27, the two mitomycins containing terminal-substituted aliphatic amine groups. Albomitomycin 34 solvolyzed 6.9 times faster than 1. The observed rate data indicated that the aniline units in 23 and 24 promoted solvolysis by modifying the C(8) quinone group to give either the C(8) hemiaminal or the C(8) imine adduct, Formation of these adducts disrupted the delocalization of the indoline N(4) electrons with the C(5a)-C(8a)-C(8)-O conjugated system, permitting the sequential activation of the C(1) site toward nucleophilic substitution. The significance of these findings for the mode of action of KW-2149 and BMS-181174 is briefly discussed.

  DOI：

  10.1021/jo970675t
• 作为产物：
  描述：

  丝裂霉素 A 、 N-苯基乙二胺 以 二氯甲烷 为溶剂， 反应 5.0h， 以99%的产率得到7-N-(2-anilinoethyl)mitomycin C
  参考文献：
  名称：

  C(7)-Substituted Diaminomitomycins:  Synthesis, Structure, and Chemical Reactivity

  摘要：

  Five mitomycins (23-27) were prepared to determine if an appended C(7) diamine substituent would promote C(1) nucleophilic substitution transformations by covalent modification of the C(8) quinone group. The appended C(7) diamine units varied in the basicity of the terminal amine and in the type and length of the carbon backbone. The mitomycins were prepared in high yield by treatment of mitomycin A (28) with selected diamines. Mitomycin 25, which contained a C(7) 3-amino-2,2-dimethylpropylamine unit, underwent rapid conversion to the corresponding albomitomycin-type adduct 34 in which the C(8) quinone group was converted to the corresponding C(8) imine. Dissolution of each mitomycin (23, 24, 26, 27, and 34) in methanol (''pH'' 5.5, 25 degrees C) led to the production of the cis- and trans-C(1) methoxymitosenes. The rates of salvolysis were monitored by HPLC and followed pseudo-first-order kinetics. Modest rate enhancements (5.1-15.2-fold), compared with mitomycin C(1), were observed for 7-N-(2-aminobenzyl)mitomycin C (23) and 7-N(2-anilinoethyl)mitomycin C(24), the two mitomycins containing terminal aniline groups. Solvolysis of 23 gave the C(1) methoxymitosenes 37 and 38, in which the C(8) site was converted to the cyclized C(8) imine; solvolysis of 24 gave C(1) methoxy products 39 and 40, in which the C(8) quinone unit was not modified. No appreciable rate enhancements over 1 were observed for 26 and 27, the two mitomycins containing terminal-substituted aliphatic amine groups. Albomitomycin 34 solvolyzed 6.9 times faster than 1. The observed rate data indicated that the aniline units in 23 and 24 promoted solvolysis by modifying the C(8) quinone group to give either the C(8) hemiaminal or the C(8) imine adduct, Formation of these adducts disrupted the delocalization of the indoline N(4) electrons with the C(5a)-C(8a)-C(8)-O conjugated system, permitting the sequential activation of the C(1) site toward nucleophilic substitution. The significance of these findings for the mode of action of KW-2149 and BMS-181174 is briefly discussed.

  DOI：

  10.1021/jo970675t

文献信息

• C(7)-Substituted Diaminomitomycins:  Synthesis, Structure, and Chemical Reactivity
  作者：Shuang Wang、Harold Kohn

  DOI：10.1021/jo970675t

  日期：1997.8.1

  Five mitomycins (23-27) were prepared to determine if an appended C(7) diamine substituent would promote C(1) nucleophilic substitution transformations by covalent modification of the C(8) quinone group. The appended C(7) diamine units varied in the basicity of the terminal amine and in the type and length of the carbon backbone. The mitomycins were prepared in high yield by treatment of mitomycin A (28) with selected diamines. Mitomycin 25, which contained a C(7) 3-amino-2,2-dimethylpropylamine unit, underwent rapid conversion to the corresponding albomitomycin-type adduct 34 in which the C(8) quinone group was converted to the corresponding C(8) imine. Dissolution of each mitomycin (23, 24, 26, 27, and 34) in methanol (''pH'' 5.5, 25 degrees C) led to the production of the cis- and trans-C(1) methoxymitosenes. The rates of salvolysis were monitored by HPLC and followed pseudo-first-order kinetics. Modest rate enhancements (5.1-15.2-fold), compared with mitomycin C(1), were observed for 7-N-(2-aminobenzyl)mitomycin C (23) and 7-N(2-anilinoethyl)mitomycin C(24), the two mitomycins containing terminal aniline groups. Solvolysis of 23 gave the C(1) methoxymitosenes 37 and 38, in which the C(8) site was converted to the cyclized C(8) imine; solvolysis of 24 gave C(1) methoxy products 39 and 40, in which the C(8) quinone unit was not modified. No appreciable rate enhancements over 1 were observed for 26 and 27, the two mitomycins containing terminal-substituted aliphatic amine groups. Albomitomycin 34 solvolyzed 6.9 times faster than 1. The observed rate data indicated that the aniline units in 23 and 24 promoted solvolysis by modifying the C(8) quinone group to give either the C(8) hemiaminal or the C(8) imine adduct, Formation of these adducts disrupted the delocalization of the indoline N(4) electrons with the C(5a)-C(8a)-C(8)-O conjugated system, permitting the sequential activation of the C(1) site toward nucleophilic substitution. The significance of these findings for the mode of action of KW-2149 and BMS-181174 is briefly discussed.