Short-Step and Scalable Synthesis of (±)-Cytoxazone

Abstract

A five-step and scalable synthesis of racemic cytoxazone, a novel cytokine modulator, was accomplished in a total yield of 51% from p-methoxycinnamyl alcohol without any protective groups. The keystep was the new one-pot azidohydroxylation procedure by the combined use of NaN₃–H₂O₂–CH₃CN. The epoxidation of an olefin by means of an in situ-formed iminohydroperoxide worked well, accompanied by the concomitant regioselective ring opening reaction of the resulting highly reactive epoxide with an azide ion.