Microwave assisted 2,5-diketopiperazine formation from protected dipeptides

ORGN 173

Ronny Lundin, ronny.lundin@eu.biotage.com and Panagiotis Ioannidis, panagiotis.ioannidis@eu.biotage.com. Biotage Sweden AB, Kungsgatan 76, SE 75318 Uppsala, Sweden
The formation of 2,5-diketopiperazines from a water suspension of N-Boc protected dipeptide alkylesters was induced by microwave assisted heating. The products, which precipitated, were obtained in good yields and required no further purification. However, racemisation or diastereomer formation was found with one or two phenylalanines in the sequence. Microwave assisted heating was likewise applied in the Boc deprotecting step as well as in the synthesis of the protected dipeptides, where polystyrene bound carbodiimide, with HOBt as additive, was used as coupling agent. Two side products, formed through alkylation of HOBt by the solvent dichloromethane at the enhanced temperature, were detected during the peptide coupling.