3-[2'-(2-aminoethyl)-2,4'-bithiazole-4-carboxamido]propyl methyl sulfide | 78175-36-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-[2'-(2-aminoethyl)-2,4'-bithiazole-4-carboxamido]propyl methyl sulfide
• 英文别名: 2-[2-(2-aminoethyl)-3H-thiazol-1-ium-4-yl]-N-(3-methylsulfanylpropyl)thiazole-4-carboxamide；2-[2-(2-aminoethyl)-1,3-thiazol-4-yl]-N-(3-methylsulfanylpropyl)-1,3-thiazole-4-carboxamide
• CAS: 78175-36-7
• 化学式: C₁₃H₁₈N₄OS₃
• 分子量: 342.51
• InChiKey: HIVIVZNWQKMPSG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  163
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-[2'-(2-aminoethyl)-2,4'-bithiazole-4-carboxamido]propyl methyl sulfide 在 二甲基硫 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 生成 2-[2-[2-[[(2S,3R)-2-amino-3-hydroxybutanoyl]amino]ethyl]-1,3-thiazol-4-yl]-N-(3-methylsulfanylpropyl)-1,3-thiazole-4-carboxamide
  参考文献：
  名称：

  博来霉素类抗生素的全合成。博来霉素去甲基 A2、博来霉素 A2 和去氨甲酰博来霉素去甲基 A2 的全合成

  摘要：

  描述了通过两种途径对博来霉素 A2 (1) 的全合成。博来霉素 A2 合成的最后一步涉及博来霉素去甲基 A2 的甲基化 (2)。这种博来霉素衍生物在机械上很受关注，并且还可以通过其已知的化学转化为博来霉素酸来提供其他博来霉素的途径。因此，所提出的合成策略代表了一种特别通用的方法，用于详细说明各种 BLM 同源物。博来霉素是由五个关键中间体构建的，描述了它们的合成。1,6-二-O-乙酰-3,4-二-O-苄基-2-O-[2,4,6-三-O-乙酰-3-O-(N-乙酰氨基甲酰基)-α-d -吡喃甘露糖基]-β-1-吡喃葡萄糖 (3) 被定量转化为其二糖氯化物 (4)，后者与 Nα 缩合，

  DOI：

  10.1021/ja9819458
• 作为产物：
  描述：

  2'-(2-Aminoethyl)-2,4'-bithiazole-4-carboxylic acid hydrochloride 在 吡啶 、 ammonium hydroxide 、 氯化亚砜 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 26.0h， 生成 3-[2'-(2-aminoethyl)-2,4'-bithiazole-4-carboxamido]propyl methyl sulfide
  参考文献：
  名称：

  Synthesis and DNA binding of [3-[2'-(2-acetamidoethyl)-2,4'-bithiazole-4-carboxamido]propyl]dimethylsulfonium chloride, a fragment of bleomycin A2

  摘要：

  [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.

  DOI：

  10.1021/jm00135a008

文献信息

• A Systematic Evaluation of the Bleomycin A₂ <scp>l</scp>-Threonine Side Chain:  Its Role in Preorganization of a Compact Conformation Implicated in Sequence-Selective DNA Cleavage
  作者：Dale L. Boger、Timothy M. Ramsey、Hui Cai、Silvia T. Hoehn、JoAnne Stubbe

  DOI：10.1021/ja9816638

  日期：1998.9.1

  The preparation and examination of 3-7 are detailed and constitute analogues of deglycobleomycin A(2) (2) containing systematic modifications in the L-threonine side chain. The studies revealed a substantial impact of the substituent on the DNA cleavage efficiency and ratio of double strand/single strand (ds/ss) cleavage without affecting the characteristic 5'-GPy selectivity. The results of the comparisons proved consistent with conformational effects of the substituent within the linker domain which restrict the number of accessible conformations (Phi congruent to -120 degrees, Psi = 60-180 degrees) and favor adoption of a compact conformation (Phi congruent to -120 degrees, Psi congruent to 180 degrees) implicated in sequence-selective DNA cleavage. The studies also identify one potential site that may adopt two nearly equivalent turn conformations. This site may constitute one swivel point in the structure that permits access to a class of related bound structures (Psi = 60-180 degrees) adaptable to variable conformational characteristics required of multiple cleavage sites, including access to both strands of duplex DNA from a single intercalation site important for both primary and secondary DNA cleavage.
• 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
• 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
  作者：Dale L. Boger、Steven L. Colletti、Takeshi Honda、Royce F. Menezes

  DOI：10.1021/ja00092a011

  日期：1994.6

  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.
• N-methyl threonine analogues of deglycobleomycin A2: Synthesis and evaluation
  作者：Dale L. Boger、Shuji Teramoto、Hui Cai

  DOI：10.1016/s0968-0896(97)00107-7

  日期：1997.8

  The synthesis of 5 and its D-allo-threonine epimer 6 and the comparison of their DNA cleavage efficiency and selectivity with that of deglycobleomycin A(2) (3) are detailed. The studies illustrate that N-methylation of the L-threonine subunit within deglycobleomycin A(2) dramatically reduces the DNA cleavage efficiency (10-15-fold), weakens and nearly abolishes the inherent DNA cleavage selectivity, but has little effect on the inherent oxidation capabilities of the activated Fe(III) complexes. The results are consistent with a previously unrecognized prominent role for the threonine NH and the potential importance of a hydrogen bond to the Fe(III) hydroperoxide complex of bleomycin or a subsequent activated complex implicated in recent structural models. (C) 1997 Elsevier Science Ltd.
• Deglycobleomycin: total synthesis and oxygen transfer properties of an active bleomycin analog
  作者：Yoshiaki Aoyagi、H. Suguna、Natesan Murugesan、Guy M. Ehrenfeld、Li Ho Chang、Tadaaki Ohgi、Mohammed S. Shekhani、Michael P. Kirkup、Sidney M. Hecht

  DOI：10.1021/ja00383a045

  日期：1982.9