Synthesis of a CCR3 Antagonist

Abstract

Significance: The CCR3 antagonist M is a potential treatment for asthma and allergic rhinitis. The synthesis depicted provided 20 kg of the target. Key steps include the asymmetric hydrogenation of B to C and the quinidine-mediated desymmetrization of the meso-anhydride E.Comment: Note the 172 mol-scale Curtius rearrangement using diphenylphosphoryl azide by which H was converted into carbamate I.

Organocatalysis in Total Synthesis

“…In this field, Yue and co-workers have disclosed the stereoselective synthesis of a CCR3 antagonist, with potential activity in the prevention of inflammation in asthma and allergic rhinitis, in 20-kg pilot-plant manufacture [124]. The authors designed its synthesis from suitable for carrying out the process on a pilot plant scale (Scheme XII.14).…”