Eliglustat is a ceramide glucosyltransferase inhibitor work as first line oral therapy for adults with Gaucher disease type 1 (a rare disease) at present. Although the eliglustat in enantiomerically pure forms is obtained by asymmetric syntheses, the reported methods suffer from many limits when it comes to industrial applications. Therefore, the preparation of a racemic mixture followed by resolution can still be a viable and straightforward alternative, especially when it could be adapted to large scale. Herein, we developed an effective and practical synthetic route to prepare stereoisomers mixture of eliglustat, and a novel chiral resolution method to prepare eliglustat. Using 1,1'-Binaphthyl-2,2'-diyl -hydrogenphosphate (BNDHP) as resolution reagent, optical pure eliglustat (e.e. > 99%, 13.97% total yield) could be obtained after recrystallization.

Eliglustat是一种神经酰胺葡糖基转移酶抑制剂，目前是成年人Gaucher疾病1型（罕见疾病）的一线口服治疗药物。尽管对映体纯形式的依格鲁司他是通过不对称合成获得的，但是在工业应用中，所报道的方法受到许多限制。因此，在制备外消旋混合物后再进行拆分仍然是可行而直接的选择，尤其是当它可以大规模应用时。本文中，我们开发了一种有效且实用的合成方法来制备依格司他的立体异构体混合物，以及一种新颖的手性拆分方法来制备依格司他。使用1,1'-联萘基-2,2'-磷酸二氢基酯（BNDHP）作为拆分试剂，使用光学纯eliglustat（ee> 99％，13。