Synthesis and conformational analysis of constrained beta-turn mimetics using a bicyclic turn inducer and the Petasis three-component reaction on solid-phase

A new set of β-turn mimetics incorporating a bicyclic turn inducer was achieved by use of the solid-phase Petasis reaction in a stereoselective fashion. The stereoselectivity of the reaction turned out to be dependent on the side chain of the amino acid preceding the reverse turn inducer. The β-turn mimetics were stabilized by strong intramolecular 10-membered ring hydrogen bonds, detected by conformational analysis by NMR and molecular modelling, whilst the turn type was controlled by the final amine component. Use of arylboronic acids provided access to chemical diversity at position i + 1, whilst the versatility of the HMBA resin allowed additional diversification to be introduced at the cleavage stage, thus providing a tool for the generation of libraries of β-turn mimetics as privileged structures in combinatorial chemistry.