6-Demethyl-7,7-(ethylenedioxy)-6,7-dihydro-6-methylidenemitosane | 122644-75-1

• 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: 6-Demethyl-7,7-(ethylenedioxy)-6,7-dihydro-6-methylidenemitosane
• 英文别名: [(4'S,6'S,7'R,8'S)-5'-acetyl-7'-methoxy-12'-methylidene-10',13'-dioxospiro[1,3-dioxolane-2,11'-2,5-diazatetracyclo[7.4.0.02,7.04,6]tridec-1(9)-ene]-8'-yl]methyl carbamate
• CAS: 122644-75-1
• 化学式: C₁₉H₂₁N₃O₈
• 分子量: 419.391
• InChiKey: IWLJRXMUAJTGLF-MECDVEOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  138
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  6-Demethyl-7,7-(ethylenedioxy)-6,7-dihydro-6-methylidenemitosane 在 氢氧化钾 硼氘化钠 作用下， 以 氘代甲醇 为溶剂， 反应 12.67h， 生成 6-methyl-²H₁>mitomycin 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
• 作为产物：
  描述：

  丝裂霉素 C 在 吡啶 、 氨 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 反应 1.25h， 生成 6-Demethyl-7,7-(ethylenedioxy)-6,7-dihydro-6-methylidenemitosane
  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

• Synthesis and Antitumor Activity of Novel Mitomycin Derivatives Containing Functional Groups at the C-6-Methyl Position
  作者：Hitoshi Arai、Yutaka Kanda、Tadashi Ashizawa、Makoto Morimoto、Katsushige Gomi、Motomichi Kono、Masaji Kasai

  DOI：10.1021/jm00038a008

  日期：1994.6

  compounds exhibited remarkable activity against MMC-resistant P388 in mice. FAB-MS spectra of these mitomycin derivatives showed the elimination of the C-6-methyl substituents from the mitomycin skeletons to form quinonemethides. Interestingly, treatment of 6-demethyl-6-[[(2-pyrimidinyl)thio]methyl ]mitomycin C (12v) with diethylamine afforded 6-demethyl-6-[(diethylamino)methyl]mitomycin C (31) in good

  合成了一系列C-6取代的甲基丝裂霉素，并评估了其抗细胞和抗肿瘤活性。这些新颖的化合物是通过将各种醇或硫醇迈克尔加成至6-去甲基-7,7-（乙二氧基）-6,7-二氢-6-亚甲基亚神经松脂中，然后用NH3或MeOH / K2CO3处理而制备的。大多数化合物对HeLa S3均有效，其中一些化合物对小鼠的P388白血病和肉瘤180显示出优于丝裂霉素C（MMC）的活性。此外，某些化合物对小鼠的MMM耐药P388表现出显着活性。这些丝裂霉素衍生物的FAB-MS光谱表明，从丝裂霉素骨架上消除了C-6-甲基取代基，从而形成了醌甲基化物。有趣的是 用二乙胺处理6-去甲基-6-[[[（2-嘧啶基）硫代]甲基]丝裂霉素C（12v）得到6-脱甲基-6-[[（二乙氨基）甲基]丝裂霉素C（31），收率高。这些结果表明，C-6取代的甲基丝裂霉素将具有与MMC不同的生物学特性。
• Mitomycin derivatives having unique condensed-ring structures. Their synthesis and antitumor activity.
  作者：HITOSHI ARAI、YUTAKA KANDA、TADASHI ASHIZAWA、MAKOTO MORIMOTO、KATSUSHIGE GOMI、MOTOMICHI KONO、MASAJI KASAI

  DOI：10.7164/antibiotics.47.1312

  日期：——

  A series of mitomycin derivatives 1-3 having unique condensed-ring structures was synthesized and evaluated for their anticellular and antitumor activity. These compounds were synthesized by the Michael addition of 1.3-dicarbonyl compounds to 6-demethyl-7,7-(ethylenedioxy)-6,7-dihydro-6-methylenemitosanes (4-6, and 14) and the subsequent cyclization. For the preparation of 1. the allyloxycarbonyl (Aloc)

  合成了一系列具有独特的稠环结构的丝裂霉素衍生物1-3，并评估了它们的抗细胞和抗肿瘤活性。这些化合物是通过将1.3-二羰基化合物迈克尔加成至6-去甲基-7,7-（亚乙二氧基）-6,7-二氢-6-亚甲基二氢呋喃酮（4-6和14）并随后环化而合成的。为了制备1.烯丙氧基羰基（Aloc）基团可用于保护氮丙啶（1a-NH），因为在温和的条件下用Pd（0）和HCO 2 H-NEt 3进行脱保护时，底物没有分解。在这些结构独特的衍生物中，化合物1a，1b，1d和1e对小鼠的HeLa S3人肿瘤细胞和肉瘤180实体瘤非常有效。
• An unusual replacement of a methylene moiety by a phenylseleno group. Synthesis of mitomycin C labelled at C-6 by 13CH3 and C2H3
  作者：Masaji Kasai、Hitoshi Arai、Yutaka Kanda

  DOI：10.1039/c39910000600

  日期：——

  A novel replacement of the C-6-methylene group of 7,7-ethylenedioxy-6-methylenemitosane by a phenylseleno group was employed to prepare a critical intermediate in the synthesis of mitomycin C labelled at C-6 by 13CH3 and C2H3.

  利用苯基硒基取代 7,7-ethylenedioxy-6-methylenemitosane 的 C-6-亚甲基这一新颖方法，制备了丝裂霉素 C 合成过程中的一个关键中间体，该中间体的 C-6 被 13CH3 和 C2H3 标记。
• Synthesis and Antitumor Activity of Novel 6-Alkyl-6-demethylmitomycins
  作者：Hitoshi Arai、Yutaka Kanda、Tadashi Ashizawa、Makoto Morimoto、Katsushige Gomi、Motomichi Kono、Masaji Kasai

  DOI：10.1021/jm00038a009

  日期：1994.6

  A series of 6-alkyl-6-demethylmitomycins (1-5) was synthesized and evaluated for anticellular and antitumor activities. These novel compounds were prepared by Michael addition of various carbanion species to 6-demethyl-7,7-(ethylenedioxy)-6,7-dihydro-6-methylidenemitosane (6 and 9) followed by treatment with NH3 or MeOH/K2CO3. Alkylation at the C-6 position of 6-demethyl-6-selenide (7) was also useful for the alternative synthesis of 6-alkyl-6-demethylmitomycins. The antitumor activity of these derivatives was evalulated, and 6-demethyl-6-ethylmitomycin A (2a) was found to exhibit excellent activity against S-180 solid tumor in mice. The structure-activity relationship is also discussed.
• 6-Demethyl-6-halo- and 6-Demethyl-6-thiomitomycins: Synthesis of Novel Mitomycin Derivatives Involving a Tandem Michael Addition/Retro-Mannich Reaction Sequence
  作者：Hitoshi Arai、Masaji Kasai

  DOI：10.1021/jo00084a028

  日期：1994.3

  Synthesis of novel 6-demethyl-6-halomitomycins (3, 4, 6, and 7) and 6-demethyl-6-thiomitomycins (5 and 8) is described from key intermediates, namely, 6-demethyl-7,7-(ethylenedioxy)-6,6-dihalo- 6,7-dihydromitosanes (18 and 19) and 6-demethyl-7,7- (ethylenedioxy)-6,7-dihydro-6-thiomitosane (20), respectively. Compounds 18-20 were prepared through a tandem Michael addition and a retro-Mannich reaction sequence (N-halosuccinimide or cationic arylsulfenyl species in the presence of Et(2)NH) on 10.