Solid-phase synthesis of partially-modified retro and retro-inverso ψ[NHCH(CF3)]-peptides

The solid-phase synthesis of a novel class of retro and retro-inverso peptides featuring a ψ[NHCH(CF3)] surrogate of the classical (NHCO) retro-peptide bond has been accomplished. Wang resin bound α-amino esters 2 were engaged in Michael-type N-additions with 3-(E-enoyl)-1,3-oxazolidin-2-one 3, which took place very effectively. Highly chemoselective exocyclic oxazolidinone cleavage, followed by parallel couplings of the resulting polymer bound pseudo-peptides 6 with further α-amino esters, and final release from the resins 7 delivered a library of nine ψ[NHCH(CF3)] retro and retro-inverso pseudo-tripeptides 8 with purity ranging from 75 to>95%.