丝裂霉素 A | 4055-39-4

• 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
• 中文名称: 丝裂霉素 A
• 中文别名: 丝裂霉素A
• 英文名称: mitomycin A
• 英文别名: [(4S,6S,7R,8S)-7,11-dimethoxy-12-methyl-10,13-dioxo-2,5-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),11-dien-8-yl]methyl carbamate
• CAS: 4055-39-4
• 化学式: C₁₆H₁₉N₃O₆
• 分子量: 349.343
• InChiKey: HYFMSAFINFJTFH-NGSRAFSJSA-N

物化性质

• 熔点：
  159-1610C (dec)
• 沸点：
  483.53°C (rough estimate)
• 密度：
  1.2205 (rough estimate)
• 溶解度：
  氯仿：微溶；甲醇：微溶
• 颜色/状态：
  RED-VIOLET CRYSTALS FROM ACETONE + CARBON TETRACHLORIDE

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  130
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  丝裂霉素 A 生成 (6-(((dimethylamino)methylene)amino)-8a-methoxy-5-methyl-4,7-dioxo-1,1a,2,4,7,8,8a,8b-octahydroazirino[2',3':3,4]pyrrolo[1,2-a]indol-8-yl)methyl hydrogen carbonimidate
  参考文献：
  名称：

  KONO, KADZUMITO;KAVANISI, MASATSUGU;SAJTO, XIROSI;SATO, AKIRA

  摘要：

  DOI：
• 作为产物：
  描述：

  丝裂霉素 C 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 以84%的产率得到丝裂霉素 A
  参考文献：
  名称：

  First preparation of mitomycins specifically labeled with deuterium at the C6-methyl position

  摘要：

  DOI：

  10.1021/jo00295a051

文献信息

• "Studies on sialic acids". Part XXIII. Studies on glycosylation of the mitomycins. Syntheses of 7-N-(4-O-glycosylphenyl)-9a-methoxymitosanes.
  作者：Kimio FURUHATA、Kanki KOMIYAMA、Haruo OGURA、Toju HATA

  DOI：10.1248/cpb.39.255

  日期：——

  Two new derivatives of glycosyl mitomycin C, 7-N-4-O-(β-D-glucopyranosyl and α-sialosyl)phenyl}-9a-methoxymitosanes, were synthesized, and their structures were elucidated by analysis of the nuclear magnetic resonance spectra. Field desorption mass spectrometry was successfully used for the confirmation of these structures. The cytotoxic, antibacterial, and antitumor activities of 7-N-(4-glycosylphenyl)-9a-methoxymitosanes were also examined.

  合成了两种新型的糖苷化米托霉素C衍生物，7-N-4-O-(β-D-葡萄糖吡喃糖基和α-神经氨酸基)苯基}-9a-甲氧基米托霉素，并通过核磁共振谱分析确证了它们的结构。成功应用场地解吸质谱法对这些结构进行了确认。同时也研究了7-N-(4-糖苷苯基)-9a-甲氧基米托霉素的细胞毒性、抗菌和抗肿瘤活性。
• Reaction of glycosyl halides with 7-hydroxy-9a-methoxymitosane sodium salt.
  作者：Kimio FURUHATA、Kanki KOMIYAMA、Kazuyoshi TAKEDA、Hiroaki TAKAYANAGI、Katsumi TORII、Katsuki MISHIMA、Haruo OGURA、Toju HATA

  DOI：10.1248/cpb.37.2651

  日期：——

  The reaction of 7-O-hydroxy-9a-methoxymitosane sodium salt with glycosyl halide derivatives gave the corresponding 7-O-glycosyl-9a-methoxymitosanes in reasonable yields. A major product, 7-O-(2, 3, 4, 6-tetra-O-acetyl-β-D-glucopyranosyl)-9a-methoxymitosane, was isolated from the reaction mixture of 7-O-hydroxy-9a-methoxymitosane sodium salt with 2, 3, 4, 6-tetra-O-acetyl-D-glucopyranosyl bromide, in addition to two minor by-products, bissaccharide derivatives of mitomycin. The structures of glycosyl derivatives of mitomycin were elucidated by analysis of the nuclear magnetic resonance spectra. Field desorption mass spectrometry was also successfully used for the confirmation of these structures. The cytocidal, antibacterial, and antitumor activities of 7-O-glycosyl-9a-methoxymitosanes were also examined.

  7-O-羟基-9a-甲氧基米托蒽醌钠盐与糖基卤代衍生物反应，以合理产率生成了相应的7-O-糖基-9a-甲氧基米托蒽醌。主要产物7-O-(2, 3, 4, 6-四-O-乙酰基-β-D-吡喃葡糖基)-9a-甲氧基米托蒽醌是从7-O-羟基-9a-甲氧基米托蒽醌钠盐与2, 3, 4, 6-四-O-乙酰基-D-吡喃葡糖基溴反应混合物中分离得到的，此外还有两个次要副产物，即米托蒽醌的双糖基衍生物。通过核磁共振光谱分析阐明了米托蒽醌糖基衍生物的结构。场解吸质谱法也成功用于这些结构的确认。同时检测了7-O-糖基-9a-甲氧基米托蒽醌的细胞毒性、抗菌和抗肿瘤活性。
• Reductive activation of mitomycins A and C by vitamin C
  作者：Manuel M. Paz

  DOI：10.1016/j.bioorg.2013.03.002

  日期：2013.6

  direct redox reduction between mitomycin C and ascorbate. To determine if this is the case, the reaction between mitomycin C and ascorbate was studied using UV/Vis spectroscopy and LC/MS. We also studied the reaction of ascorbate with mitomycin A, a highly toxic member of the mitomycin family with a higher redox potential than mitomycin C. We found that ascorbate is capable to reduce mitomycin A efficiently

  抗癌药物丝裂霉素C在通过还原活化转变为高反应性双亲电子试剂后产生细胞毒性作用，该反应是细胞中多种1电子或2电子氧化还原酶可以进行的反应。文献中的一些报道表明抗坏血酸可以调节丝裂霉素C的细胞毒性作用，从而增强或抑制其作用。由于抗坏血酸是已知能够还原醌的还原剂，因此观察到的调节作用可能是丝裂霉素C和抗坏血酸之间直接氧化还原还原的结果。为了确定是否存在这种情况，使用紫外线/可见光谱和LC / MS研究了丝裂霉素C和抗坏血酸之间的反应。我们还研究了抗坏血酸与丝裂霉素A的反应，丝裂霉素家族的高毒性成员，其氧化还原电位高于丝裂霉素C。我们发现抗坏血酸能够有效还原丝裂霉素A，但其还原丝裂霉素C的效率很低。基于还原的动力学和对反应后形成的亚油基衍生物的分析，已经阐明了活化的机理。我们发现激活是通过三种不同的机制相互作用而发生的，这三种机制的作用取决于反应的pH值。由于在生理相关的pH值下抗坏血酸对丝裂霉素
• 7-<i>N</i>-(Mercaptoalkyl)mitomycins:  Implications of Cyclization for Drug Function
  作者：Younghwa Na、Shuang Wang、Harold Kohn

  DOI：10.1021/ja0124313

  日期：2002.5.1

  and Bristol-Myers Squibb companies reported that select mitomycin C(7) aminoethylene disulfides displayed improved pharmacological profiles compared with mitomycin C (1). Mechanisms have been advanced for these mitomycins that differ from 1. Central to many of these hypotheses is the intermediate generation of 7-N-(2-mercaptoethyl)mitomycin C (5). Thiol 5 has been neither isolated nor characterized

  Kyowa Hakko Kogyo 和 Bristol-Myers Squibb 公司报告说，与丝裂霉素 C (1) 相比，选择的丝裂霉素 C(7) 氨基乙二硫醚显示出更好的药理学特征。这些丝裂霉素的机制与 1 不同。其中许多假设的核心是 7-N-（2-巯基乙基）丝裂霉素 C (5) 的中间代。硫醇 5 既没有被分离也没有被表征。为丝裂霉素 (porfiromycin) C(7)-取代的硫醇开发了两种有效的方法。在第一种方法中，硫醇是通过硫醇介导的二硫化物交换过程产生的，使用活化的混合丝裂霉素二硫化物。在第二条路线中，硫醇是通过碱介导裂解卟啉霉素 C(7)-取代的硫醇酯产生的。我们选择了四种硫醇，7-N-（2-巯基乙基）丝裂霉素 C (5)，7-N-（2-巯基乙基）卟啉霉素（12）、7-N-（2-巯基-2-甲基丙基）丝裂霉素C（13）和7-N-（3-巯基丙基）卟啉霉素（14），用于研究. 硫醇
• 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。