A flexible route to immunosuppressive agent FR252921. Asymmetric total synthesis of its (13R,14R,19R)-isomer

A flexible route to the proposed structure of FR252921, a novel immunosuppressive agent, is developed. The key elements include the assembly of its two β-hydroxy acid residues via asymmetric aldol condensation of N-acylthiazolidinethinones with aldehydes, and its triene part via a CuI/N,N-dimethylglycine catalyzed Sonogashira coupling and subsequent isomerization. Using this strategy (13R,14R,19R)-FR252921 is elaborated.