2-[2-[2-[(2,2,2-三氟乙酰基)氨基]乙基]-1,3-噻唑-4-基]-1,3-噻唑-4-羧酸 | 76275-91-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-[2-[2-[(2,2,2-三氟乙酰基)氨基]乙基]-1,3-噻唑-4-基]-1,3-噻唑-4-羧酸
• 英文名称: 2'-<2-(trifluoroacetamido)ethyl>-2,4'-bithiazole-4-carboxylic acid
• 英文别名: 2'-(2-Trifluoroacetamidoethyl)-2,4'-bithiazole-4-carboxylic acid；2'-[2-(2,2,2-Trifluoroacetamido)ethyl][2,4'-bi-1,3-thiazole]-4-carboxylic acid；2-[2-[2-[(2,2,2-trifluoroacetyl)amino]ethyl]-1,3-thiazol-4-yl]-1,3-thiazole-4-carboxylic acid
• CAS: 76275-91-7
• 化学式: C₁₁H₈F₃N₃O₃S₂
• 分子量: 351.33
• InChiKey: JQEDRNGHFOYUHC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  149
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  2-[2-[2-[(2,2,2-三氟乙酰基)氨基]乙基]-1,3-噻唑-4-基]-1,3-噻唑-4-羧酸 在 氯化亚砜 、 (CH₃)2N(C₆H₄N) 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 生成 N-(3-bromopropyl)-2-[2-[2-[(2,2,2-trifluoroacetyl)amino]ethyl]-1,3-thiazol-4-yl]-1,3-thiazole-4-carboxamide
  参考文献：
  名称：

  Bleomycin: synthesis and structural verification of the tripeptide S and tetrapeptide S moieties

  摘要：

  DOI：

  10.1021/ja00524a055
• 作为产物：
  描述：

  methyl 2-(2-bromoacetyl)thiazole-4-carboxylate 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 15.0h， 生成 2-[2-[2-[(2,2,2-三氟乙酰基)氨基]乙基]-1,3-噻唑-4-基]-1,3-噻唑-4-羧酸
  参考文献：
  名称：

  Total Synthesis of Bleomycin A2 and Related Agents. 1. Synthesis and DNA Binding Properties of the Extended C-Terminus: Tripeptide S, Tetrapeptide S, Pentapeptide S, and Related Agents

  摘要：

  Full details of concise, diastereocontrolled syntheses of 2-5 and their incorporation into tri-, tetra-, and pentapeptide S, the C-terminus of bleomycin Alt are described. The extension of the studies to the synthesis of a complete set of tri- and tetrapeptide S structural analogs 29a,b and 43b-j is detailed, and their DNA binding constants (apparent K-B, calf thymus DNA) and apparent binding site sizes were determined. Consistent with past observations, the studies highlight the fact that the majority of the DNA binding affinity for bleomycin A(2) (1.0 X 10(5) M(-1)) and deglycobleomycin Aa (1.1 x 10(5) M(-1)) is embodied within N-BOC-tripeptide S (0.26 X 10(5) M(-1)). The additional comparisons of 29a (O.18 x 10(5) M(-1)), N-BOC-tetrapeptide S (0.21 x 10(5) M(-1)), 43h (0.20 x 10(5) M(-1)), and N-BOC-pentapeptide S (0.23 X 10(5) M(-1)) versus N-BOC-dipeptide S (0.10 x 10(5) M(-1)) indicate productive stabilizing binding interactions for the tripeptide S L-threonine subunit and substituent, illustrate that the entire pentanoic acid subunit of tetrapeptide S and its substituents do not significantly contribute to DNA binding affinity, and indicate that the entire beta-hydroxy-L-histidine subunit of pentapeptide S does not contribute to DNA binding affinity. With the exception of the L-threonine side chain substituent, the observations suggest that the tri- and tetrapeptide S substituent effects on the bleomycin A(2) DNA cleavage reaction are not due to substantial stabilizing binding interactions with duplex DNA. In addition, the measured apparent binding site sizes for bleomycin A(2)(3.8 base pairs), deglycobleomycin A(2) (3.9 base pairs), N-BOC-tripeptide S (3.6 base pairs), N-BOC-tetrapeptide S (3.7 base pairs), 43h (3.5 base pairs), and N-BOC-pentapeptide S (4.2 base pairs) versus N-BOC-dipeptide S (2.2 base pairs) and 29a (2.7 base pairs) suggest that it is the tripeptide S subunit of bleomycin A(2) that is fully bound to duplex DNA, that the tripeptide S L-threonine hydroxyethyl substituent detectably affects the agent interaction with duplex DNA, but that the presence or absence of the other tetrapeptide S and pentapeptide S backbone substituents do not substantially alter the binding site size or tripeptide S binding mode.

  DOI：

  10.1021/ja00092a011

文献信息

• Synthesis of tri- and tetrapeptide S: the extended C-terminus of bleomycin A2
  作者：Dale L. Boger、Royce F. Menezes

  DOI：10.1021/jo00042a003

  日期：1992.7

  Concise diastereocontrolled syntheses of tri- and tetrapeptide S, key subunits
• Synthesis and biological activity of modified fragments of the antibiotic bleomycin A2
  作者：S. E. Bannikov、G. P. Andronnikova、N. S. Vyrupaeva、E. N. Glibin、Z. V. Pushkareva

  DOI：10.1007/bf00765216

  日期：1983.2
• Synthesis and DNA binding of [3-[2'-(2-acetamidoethyl)-2,4'-bithiazole-4-carboxamido]propyl]dimethylsulfonium chloride, a fragment of bleomycin A2
  作者：Ted T. Sakai、James M. Riordan、Thomas E. Booth、Jerry D. Glickson

  DOI：10.1021/jm00135a008

  日期：1981.3

  [3-[2'-(2-Acetamidoethyl)-2,4'-bithiazole-4-carboxamido]propyl]dimethylsulfonium chloride (1), the acetyl derivative of the cationic terminal dipeptide of bleomycin A2, has been synthesized and its binding to DNA and poly(dA-dT) has been studied by proton NMR and fluorescence spectroscopy. The spectral perturbations which occur upon binding of the compound to either nucleic acid indicate that that portion of bleomycin which binds to the nucleic acid can, for the most part, be mimicked by the fragment. The data are discussed in terms of the structure of the drug and the drug-nucleic acid complex.