1,2-cis-1-hydroxy-2-methylamino-7-aminomitosene | 92761-62-1

• 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: 1,2-cis-1-hydroxy-2-methylamino-7-aminomitosene
• 英文别名: cis-1-hydroxy-2-(methylamino)-7-aminomitosene；Porfiromycin metabolite M4；[(2S,3S)-6-amino-3-hydroxy-7-methyl-2-(methylamino)-5,8-dioxo-2,3-dihydro-1H-pyrrolo[1,2-a]indol-4-yl]methyl carbamate
• CAS: 92761-62-1
• 化学式: C₁₅H₁₈N₄O₅
• 分子量: 334.332
• InChiKey: JREJOMLMGXCYLK-CPFSXVBKSA-N

物化性质

• 沸点：
  696.7±55.0 °C(Predicted)
• 密度：
  1.74±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  150
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-methyl-7-aminoaziridinomitosene 、 水 生成 1,2-cis-1-hydroxy-2-methylamino-7-aminomitosene
  参考文献：
  名称：

  HAN, INSOOK;KOHN, HAROLD, J. ORG. CHEM., 56,(1991) N5, C. 4648-4653

  摘要：

  DOI：

文献信息

• A systematic study on the chemical stability of mitomycin A and mitomycin B.
  作者：Jos H. BEIJNEN、OEDS A.G.J. VAN DER HOUWEN、HILDE ROSING、WILLY J.M. UNDERBERG

  DOI：10.1248/cpb.34.2900

  日期：——

  The kinetics and mechanisms of the degradation of mitomycin A and mitomycin B in aqueous solution were investigated by means of ultraviolet (UV) spectrophotometry and high-performance liquid chromatography (HPLC). The influences of pH, buffers and temperature on the degradation were quantified. Degradation products were isolated and characterized by mass spectrometry (MS), UV-VIS spectrophotometry, chromatography and circular dirchroism (CD) spetroscopy. The degradation reactions follow (pseudo) first-order kinetics. The collected kinetic data allowed an accurate determination of the pKa value of the aziridine moiety of the mitomycins by using computerized curve-fitting models.

  通过紫外（UV）分光光度法和高性能液相色谱（HPLC）研究了丝裂霉素A和丝裂霉素B在水溶液中的降解动力学和机理。定量分析了pH值、缓冲液和温度对降解的影响。通过质谱（MS）、紫外-可见分光光度法、色谱法和圆二色谱（CD）光谱法分离和鉴定了降解产物。降解反应遵循（准）一级动力学。收集的动力学数据通过计算机化曲线拟合模型准确测定了丝裂霉素中氮丙啶部分的pKa值。
• Studies on the mechanism of mitomycin C(1) electrophilic transformations: structure-reactivity relationships
  作者：Insook Han、David J. Russell、Harold Kohn

  DOI：10.1021/jo00032a037

  日期：1992.3

  Previous studies have demonstrated that reductive activation of mitomycin C (1) under acidic conditions furnished high yields of the C(1) electrophilic product 2,7-diaminomitosene (5). This adduct was also the major metabolite produced upon administration of 1 to HT-29 cytosol, purified HT-29 colon carcinoma cells, and rat hepatic DT-diaphorase. Proton capture at C(1) in 1 is known to proceed with high stereoselectivity. Information concerning the mechanism and the controlling factors that govern this transformation have been determined by examining the structure-reactivity relationship for mitomycin C (1), 10-decarbamoylmitomycin C (10), N(1a)-methyl-10-decarbamoyl-10-acetoxymitomycin C (11), mitomycin D (12), 10-decarbamoylmitomycin D (13), 7-aminoaziridinomitosene (14), N(1a)-(methanesulfonyl)mitomycin C (15), and N(1a)-(toluenesulfonyl)mitomycin C (16). The combined results obtained were consistent with the hypothesis that mitomycin C C(1) electrophilic reactions funneled through quinone methide 4. The high stereoselectivity of this process has been attributed (in part) to the protonated C(2) amino group in 4. In this scenario, proton capture occurred preferentially from the site opposite to the C(2) ammonium group in order to minimize adverse coulombic interactions.
• 7-Aminoaziridinomitosenes: synthesis, structure, and chemistry
  作者：Insook Han、Harold Kohn

  DOI：10.1021/jo00015a016

  日期：1991.7

  7-Aminoleucoaziridinomitosene (2a) has been proposed as a key intermediate in the reductive activation process for the antineoplastic agent, mitomycin C (1a). Little is known about 2a and its oxidized equivalent, 7-aminoaziridinomitosene (3a). An expedient electrochemical procedure for 3a and the corresponding N-methyl analogue 3b has been developed. NMR spectral studies of 3a in DMF-d7 and DMSO-d6 provided important information concerning the solution-state structure for this adduct. Factors controlling the aziridine ring-opening process under reductive and nonreductive conditions have been determined, as well as evidence for the intermediacy of 2a in the reductive activation cascade of 1a.