An efficient total synthesis of a sphingosine-1-phosphate receptor agonist KRP-203

An efficient total synthesis of the S1P1 agonist, KRP-203, is described. The key step involves the conjugate addition of diethyl acetamidomalonate to a styrene compound to give the core structure of KRP-203. Multigram quantities of the targeted KRP-203, sufficient for several biological studies, were obtained in six steps with an overall yield of 58%.