双烟酰基取代的类环肽合成及对二价铜离子的配位研究

Synthesis of Nicotinoyl Disubstituted Pseudo-cyclopeptide and Its Coordination Behavior with Cu^(2+)

在模拟蛋白质的分子识别功能方面, 人工合成以氨基酸为主要结构单元的环肽由于更接近于生命物质, 因此作为主体分子来模拟生命现象更贴切. 目前, 这方面的研究主要集中在环肽对碱金属、碱土金属以及磷酸酯的识别或跨膜传输等方面[1～6]. 环肽通过骨架或侧臂与过渡金属离子的配位研究也仅有几例[7～10]. 实际上, 许多过渡金属, 如Cu(Ⅱ), Zn(Ⅱ)和Fe(Ⅱ) 等在稳定蛋白质的构象及增强其催化活性方面发挥着重要的作用. 因此, 设计合成能有效识别过渡金属离子的环肽分子, 并研究其离子配位行为, 对于探明酶的作用机理可能具有更直接的意义.

A 26-membered nicotinoyl disubstituted cyclopseudopeptide was synthesized through a simple six-step prvcedure(Scheme 1) with cystine dimethyl ester, iminodiacetic acid, and nicotinoyl chloride hy-drochloride as the starting materials. The structure of the key intermediates 4 and 5 was verified by 1H NMR and FAB-MS, and that of the final product 7 by 'H NMR, IR, FAB-MS and elemental analysis. Subsequent treatment of 7 with Cu(ClO4)z gives a mononuclear cuprate(Ⅱ ) complex whose structure was characterized by IR, FAB-MS. The quick formation of the cuprate-cyclopeptide complex demonstrates that the title peptide can serve as a good reception in Cu( Ⅱ ) recognition.