Author/Authors :
Haiming Zhang ، نويسنده , , Jie Yan، نويسنده , , Mark S. Bednarz، نويسنده , , Gonzalo Hernandez، نويسنده , , Yuelie Lu، نويسنده , , Lawrence F. Courtney، نويسنده , , Jen-Yen Jason Chen، نويسنده , , Weifeng Hu، نويسنده , , Renmao Liu، نويسنده , , Xiaogen Yang، نويسنده , , Wenxue Wu، نويسنده ,
Abstract :
A practical and scalable synthesis of in vivo sphingosine-1-phosphate lyase inhibitor LX2931 (1) is described. The synthetic route features an improved Büchi cyclocondensation of 2-ethoxyacrylonitrile (3) with either 1-amino-1-deoxy-d-fructose acetate (4a) or d-(+)-glucosamine hydrochloride (4b) to produce 1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone (2, THI), followed by oximation of THI and acid-promoted oxime isomerization to give LX2931 (1).
Keywords :
Cyclocondensation , Oxime isomerization , Glucosamine , Fructosamine , Sphingosine-1-phosphate
