10-去氨基甲酰丝裂霉素 C | 26909-37-5

• 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: 10-去氨基甲酰丝裂霉素 C
• 中文别名: 10-去氨基甲酰丝裂霉素C；-磷酸(2:1)乙基汞
• 英文名称: decarbamoylmitomycin C
• 英文别名: 10-decarbamoylmitomycin C；(4S,6S,7R,8S)-11-amino-8-(hydroxymethyl)-7-methoxy-12-methyl-2,5-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),11-diene-10,13-dione
• CAS: 26909-37-5
• 化学式: C₁₄H₁₇N₃O₄
• 分子量: 291.307
• InChiKey: OUADMZZEIRSDSG-NKFUZKMXSA-N

物化性质

• 沸点：
  433.32°C (rough estimate)
• 密度：
  1.1974 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  115
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  10-去氨基甲酰丝裂霉素 C 在 5% Pd/C 、 氢气 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 以90%的产率得到10-decarbamoyl-2,7-diaminomitosene
  参考文献：
  名称：

  丝裂霉素 C 寡聚脱氧核糖核苷酸加合物的后寡聚化法合成三氨基丝裂

  摘要：

  癌症化学治疗剂丝裂霉素 C (MC) 在体内和体外单功能和双功能地烷基化和交联 DNA，形成六种已知结构的主要 MC-脱氧鸟苷加合物。通过后寡聚化方法合成一个单加合物 (8) 在核苷和寡核苷酸水平上完成，后者导致 8 位点特异性放置在 12 聚体寡脱氧核糖核苷酸 26 中。这是该方法的首次应用一种合成复杂天然产物 DNA 加合物的方法。必需的选择性保护的三氨基丝氨酸 14 和 24 的制备开始于从 MC 中去除 10-氨基甲酰基，然后还原转化为 10-decarbamoyl-2,7-diaminomitoseene 10。该物质在几个步骤中转化为 14 或 24。两者都成功地与 12 聚体寡核苷酸的 2-氟-O(6)-(2-三甲基甲硅烷基乙基) 脱氧肌苷残基偶联。与 12 聚体寡核苷酸偶联后的 N(2)-苯乙酰基保护基团 14 不能按预期被青霉素酰胺酶去除。然而，与 12 聚体寡核苷酸偶联后的

  DOI：

  10.1021/ja802118p
• 作为产物：
  描述：

  丝裂霉素 C 在 sodium methylate 作用下， 以 甲醇 、 苯 为溶剂， 以80%的产率得到10-去氨基甲酰丝裂霉素 C
  参考文献：
  名称：

  Synthesis of N-Substituted 10-Des(carbamoyloxy)-10-azidomitomycins

  摘要：

  已开发出一种合成N-取代的10-脱(氨甲酰氧基)-10-叠氮基丝裂霉素5的通用方法。这些化合物预期能迅速转化为相应的C-10异硫氰酸酯衍生物，使丝裂霉素能够与生物分子耦合。关键的合成中间体是10-脱(氨甲酰氧基)-10-叠氮基丝裂霉素C（12）。化合物12是通过丝裂霉素C（1）的去氨甲酰化，随后用芴甲氧羰基氯进行氮丙啶保护，以及用甲磺酰氯激活C-10位点制备的。通过用吗啉脱除芴甲氧羰基单元并处理叠氮化钠得到12。

  DOI：

  10.1055/s-1997-1297

文献信息

• Lack of influence of the carbamoyl group on the stereochemistry of the acid-catalyzed opening of the aziridine ring of the mitomycins and of congeners
  作者：Ulfert Hornemann、Paul J. Keller、Kazuyoshi Takeda

  DOI：10.1021/jm00379a008

  日期：1985.1

  be stable when treated with acid under the conditions of its formation. Mitomycin B was also shown to yield predominantly the cis product when it was subjected to acid-catalyzed opening of its aziridine ring. The 1H NMR spectra of acetate derivatives prepared from mitomycin B show two sets of signals that are due to two populations of rotamers. The analysis of these spectra has substantiated several

  已知丝裂霉素A和C的氮丙啶环的酸催化开环主要通过顺式立体化学发生。我们已经观察到丝裂霉素C的C-10及其某些类似物中氨基甲酰基的存在或不存在对该开环的立体化学没有显着影响。从丝裂霉素C获得的反式产物显示出在形成条件下用酸处理时是稳定的。当丝裂霉素B经过其氮丙啶环的酸催化的打开时，它也显示出主要产生顺式产物。由丝裂霉素B制备的乙酸酯衍生物的1 H NMR光谱显示出两组信号，这是由于两个群体的旋转异构体引起的。这些光谱的分析证实了先前的几个光谱分配。
• Isolation and Rationale for the Formation of Isomeric Decarbamoylmitomycin C-<i>N</i>⁶-deoxyadenosine Adducts in DNA
  作者：Owen Zacarias、William Aguilar、Manuel M. Paz、Sergey Tsukanov、Maggie Zheng、Shu-Yuan Cheng、Padmanava Pradhan、Elise Champeil

  DOI：10.1021/acs.chemrestox.8b00102

  日期：2018.8.20

  digestion of the alkylated DNA substrates. Results revealed the following rules for DMC dA alkylation: (i) DMC dA adducts are formed at a 48- to 4-fold lower frequency than dG adducts, (ii) the 5′-phosphodiester linkage of the dA adducts is resistant to snake venom diesterase, (iii) end-chain dA residues are more reactive than internal ones in duplex DNA, and (iv) nucleophilic addition by dA occurs on

  丝裂霉素 C (MC) 是一种抗癌剂，可烷基化 DNA 形成单加合物和链间交联。去氨甲酰丝裂霉素 C (DMC) 是 MC 的类似物，C10 上缺少氨基甲酸酯。从用MC和DMC处理培养细胞中分离出的主要DNA加合物是N 2 -脱氧鸟苷(dG)加合物，并且在dG-线粒体键处采用相反的立体化学构型。为了阐明 DMC-DNA 烷基化的分子机制，我们使用仿生条件使短寡核苷酸、小牛胸腺和藤黄杆菌DNA 与 DMC 发生反应。这些实验表明，DMC 能够在双功能还原条件下和低温下与 DNA 形成两种立体异构脱氧腺苷 (dA) 加合物。烷基化 DNA 底物酶消化后，通过 HPLC 分析检测和定量形成的 dA-DMC 加合物。结果揭示了 DMC dA 烷基化的以下规则：(i) DMC dA 加合物的形成频率比 dG 加合物低 48 至 4 倍，(ii) dA 加合物的 5'-磷酸二酯键可抵抗蛇毒二酯酶，(iii)
• C(10) Halogen 10-Des(carbamoyloxy)porfiromycins: Synthesis, Chemistry, and Biological Activity
  作者：Daeock Choi、Byungwoo Yoo、Kimberly L. Colson、Gary E. Martin、Harold Kohn

  DOI：10.1021/jo00116a024

  日期：1995.6

  An efficient four-step procedure for the preparation of C(10) halogen 10-des(carbamoyloxy)porfiromycins 3-5 beginning with mitomycin C(1) is described. Solvolytic removal (NaOMe, MeOH/benzene) of the C(10) carbamoyl group in 1 followed by N-methylation (dimethyl sulfate (15 equiv), 1,8-bis(dimethylamino)naphthalene (15 equiv) in THF) provided 10-decarbamoylporfiromycin (7) in 65% yield. Treatment of 7 with methanesulfonyl chloride in pyridine gave 10-decarbamoyl-10-methanesulfonylporfiromycin (8) in 83% yield, which upon heating with metal halides (i.e., LiCl, LiBr, NaI) in either DMF or ethylene glycol dimethyl ether furnished the C(10) halogen 10-des(carbamoyloxy)porfiromycins 3-5 in 68-81% yields. The C(10) halogen 10-des(carbamoyloxy)porfiromycins served as useful starting materials for C(10)-modified derivatives. Treatment of the C(10) bromo derivative 4 with 1,8-diazabicyclo[5.4.0]undec-7-ene provided the elimination product, 10-des(carbamoyloxy)-9-dehydroporfiromycin (12), while addition of AgSCN to the C(10) iodo porfiromycin 5 led to the substituted adducts 10-des(carbamoyloxy)-10-thiocyanatoporfiromycin (10) and 10-des(carbamoyloxy)-10-thiocyanato-9-epi-mitomycin D (11). The C(10) halogen 10-des(carbamoyloxy)porfiromycins also underwent novel radical and thermal skeletal rearrangements. Treatment of the C(10) iodo derivative 5 with tributyltin hydride and AIBN led to the production of the ring-expanded quinone 14. Thermolysis of the C(10) bromo (4) and the C(10) iodo (5) adducts gave the tetracycles 18 and 19, respectively, in which the C(2) nitrogen bond in the starting porfiromycin had been preferentially cleaved in favor of the C(1) bond. Potential pathways for these rearrangements are briefly outlined. The in vitro cytotoxicities of 3-5 in human colon carcinoma cell lines were evaluated. All three C(10) halogen 10-des(carbamoyloxy)porfiromycins were noticeably less potent than mitomycin C.
• 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.
• Chromium(II) perchlorate: an effective reagent for the preparation of mitomycin C nucleophilic substituted compounds
  作者：Y. P. Hong、Harold Kohn

  DOI：10.1021/jo00022a049

  日期：1991.10