带不同侧链的含L-DOPA环二肽的合成及其DPPH自由基清除活性的测试

Synthesis of L-DOPA-Containing Cyclodipeptides with Versatile Side-Chains and DPPH Radical Scavenging Activity

本文采用了一种温和的合成策略成功地制备了L-DOPA与侧链含羟基的Thr或含羧基的Asp形成的环二肽.另外,以Val为例,本文又探索了一种新的合成含多巴环二肽的路线,即采用常见易得的N-Fmoc保护的氨基酸与多巴甲酯中间体H-DOPA(Acetonide)-OMe反应,生成多巴在C-端的直链二肽甲酯,然后再在哌啶催化下进行成环反应,该方法避免了使用价格昂贵或难以购买到的氨基酸甲酯作为反应物.采用上述合成策略,本文制备了三个全新的含多巴的环二肽:即cyclo(DOPA-Thr)、cyclo(DOPA-Asp)和cyclo(DOPA-Val).进一步的活性测试表明,所合成的含多巴的环二肽具有一定的DPPH自由基清除能力,其IC50与维生素C的值相当.

In the report, a milder synthetic protocol was performed to prepare cyclodipeptides formed by L-DOPA and hydroxyl group-containing side chain Thr and carboxyl groups-containing side chain Asp. Val was used as an example to explore an alternative method to prepare a linear dipeptide with L-DOPA on the C-terminal, in which a readily-available N-Fmoc protected amino acid was reacted with an H-DOPA(Acetonide)-OMe intermediate, a linear dipeptide methyl ester with L-DOPA on the N-terminal was prepared, and the piperidine-promoted cyclization of the linear molecule at room temperature occurs. The synthetic strategy can lead to the production of three new cyclodipeptides, cyclo(DOPA-Thr), cyclo(DOPA-Asp), and cyclo(DOPA-Val). The further activity tests show that those L-DOPA-containing cyclodipeptides are capable of scavenging DPPH radicals with low IC50 values close to that of vitamin C.