氯化血红素-空气催化氧化体系应用于利那洛肽的合成

摘要

目的 使用氯化血红素催化氧化的方法合成利那洛肽.方法 采用9-芴甲氧头羰基(Fmoc)固相合成策略,以Wang树脂为载体和三苯甲基(Trt)为保护基的半胱氨酸合成利那洛肽线性肽,使用氯化血红素-空气催化氧化体系一步氧化法构建3对二硫键,并与传统的空气、二甲基亚砜和碘(I2)氧化法进行了对比.结果和结论 相对于传统氧化法,氯化血红素催化氧化法可更快速、更高效地得到目标利那洛肽,为多肽合成中的二硫键形成提供一种新的方法.%Objective To use hemin as a catalyst in the formation of disulfide bonds in the synthesis of linaclotide. Methods The linaclotide peptide was synthesized by the standard 9-fluorenylmethyl(Fmoc)solid-phase synthetic strategy. Wang resin and Trt-protected cysteine were used in the synthesis. Hemin was used in random oxidation of line linaclotide. The result was compared with those of air,dimethyl sulfoxide(DMSO),and I2 oxidation systems. Results and Conclusion Hemin is a highly effective catalyst for disulfide bond formation in linaclotide synthesis. It overcomes some disadvantages in oxidation reactions with conventional oxidative re-agents,and supplies a convenient way for the synthesis of peptide with concentrated disulfide bonds.