Department of New Drug Research and Development, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, 100050 Beijing, China.
Department of New Drug Research and Development, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, 100050 Beijing, China.
Bioorg Med Chem Lett. 2020 Aug 15;30(16):127209. doi: 10.1016/j.bmcl.2020.127209. Epub 2020 Apr 25.
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.
依利格鲁司他是一种神经酰胺葡萄糖基转移酶抑制剂,目前被用作 1 型戈谢病(一种罕见病)成人患者的一线口服治疗药物。尽管对映体纯形式的依利格鲁司他可以通过不对称合成获得,但报道的方法在工业应用方面存在许多限制。因此,制备外消旋混合物然后进行拆分仍然是一种可行且直接的替代方法,特别是当其可以适应大规模生产时。在此,我们开发了一种有效且实用的合成路线来制备依利格鲁司他的立体异构体混合物,并找到了一种新的手性拆分方法来制备依利格鲁司他。使用 1,1'-联萘-2,2'-二基-二氢膦酸(BNDHP)作为拆分试剂,经过重结晶后可以得到光学纯的依利格鲁司他(ee 值>99%,总收率为 13.97%)。