阿利克仑的合成

Synthesis of aliskiren

对肾素抑制剂阿利克仑的合成工艺进行研究。采用化学拆分法分别制备了合成阿利克仑的手性片段化合物1和2,再经5步汇聚式合成得到目标产物阿利克仑,总收率15.6%。中间体和目标产物经熔点、NMR、ESI-MS表征。所采用的工艺路线光学纯度可控,收率较好,操作简便,无需特殊试剂和复杂的分离纯化过程,具备一定的工业化生产潜力。

This paper describes a practical process for the preparation of aliskiren. Chiral building blocks 1 and 2 were prepared by chemical resolution, and a following five-step convergent synthesis led to aliskiren with an over- all yield of 15.6%. The intermediates and the target compound were characterized by melting points, NMR and MS. The convergent synthetic process of aliskiren highlights reasonable yields, ease of operation, high stereoselectivity as well as only one chromatographic purification, and thus should be amenable to large-scale production.