赖氨酸衍生氮杂大环化合物的固相合成

Solid-phase Synthesis of Aza-macrocyclic Compounds Derived from Lysine Residues

基于固相载体的假稀释效应,设计并合成了由赖氨酸为前体结构衍生的氮杂大环化合物8,9,10,12及13.合成中的关键构件是在固相树脂上肽链的N端键合的二个相邻的赖氨酸残基,并以溴乙酸为桥连组份,先后经酰化及亲核取代(SN2)反应完成三氮杂十六元环骨架的构建.5种粗产物的总收率在68.9%～86.1%之间,并全部经氨基酸组成分析及ESI-MS分析表征.

Triaza-macrocyclic compounds, based on the pseudo-dilution effect on solid support, were designed and synthesized. The key building blocks for cyclization were two lysine residues and bromoacetic acid as the bridging components via acylation-S(N)2 reaction in sequence. By present procedure, five target compounds 8, 9, 10, 12 and 13 with trinitrogen atoms in a 16-membered ring were obtained in good overall yields of 68.9%∼ 86.1% and characterized by amino acid analysis and ESI-MS.