Solid supported high-throughput organic synthesis of peptide β-turn mimetics via tandem Petasis reaction/diketopiperazine formation

High-throughput organic synthesis of bicyclic diketopiperazines 1, β-turn mimetics, is described. Starting from Merrifield resin-bound piperazine-2-carboxylic acid, first two (R4 and R5) side chains are introduced via the Petasis reaction and subsequent amide bond formation. Unblocking the α-amino group of piperazine-2-carboxylic acid, Boc-N-protected α-amino acid coupling and deprotection followed by cyclative cleavage introduces the remaining R2 and R1 side chains.