阿利吉仑不对称合成研究进展

Research progress on the asymmetric synthesis of aliskiren

阿利吉仑是由诺华公司研发的首个口服非肽类肾素抑制剂,因其良好的降压效果受到广泛关注。由于阿利吉仑分子结构中有4个手性中心,立体选择性合成的难度较大。本文综述了近年来阿利吉仑的不对称合成进展,根据关键手性中间体的来源,分手性源合成法和手性助剂法加以总结。详细分析了各合成路线的关键步骤,讨论了各方法的优缺点,以期为阿利吉仑的工业化合成提供参考。

Aliskiren, developed by Novartis, is the first non-peptide oral renin inhibitor that has attracted considerable attention due to its outstanding antihypertensive efficacy. The stereoselective synthesis of aliskiren is relatively difficult caused by the multi-chiral centers of its structure. In this review, the recently progression of synthetic methods of aliskiren was summarized as chiral pool approach and chiral auxiliary according to the source of key chiral intermediates. Key steps of each approach were analyzed and the merits and demerits were discussed. Finally, the future work and the trends of development in the synthesis of aliskiren were proposed.