Hydrothermal, catalyst-free production of a cyclic dipeptide from lysine

The formation of cyclic dipeptides, 2,5-diketopiperazines (DKP), from lysine in aqueous solution was investi-gated at hydrothermal conditions (250-350 degrees C) without the addition of catalyst. The products obtained were analyzed by GC-MS combined with extensive 1H,13C NMR analysis, after purification via preparative chroma-tography. The main product of the conversion of lysine, octahydrodipyrido[1,2-a:1 ',2 '-d]pyrazine-6,12(2H,6aH)-dione, was successfully isolated and identified. The purification/separation protocol is rapid, environmentally friendly, and highly efficient with excellent selectivity (81 wt%) in the oils obtained from the conversion of lysine at 300 degrees C. Performing the conversion step at higher temperatures or lysine concentrations led to the formation of complicated side products. Based on the evolution of key compounds during hydrothermal conversion of lysine, we propose a tentative mechanism for the formation of diketopiperazine. The technique presented in this work provides a novel catalyst-free pathway for the synthesis of DKP.

Automated summary

The formation of cyclic dipeptides from lysine in aqueous solution without the addition of catalyst was investigated at high temperature conditions. The main product, octahydrodipyrido[1,2-a:1 ',2 '-d]pyrazine-6,12(2H,6aH)-dione, was successfully isolated and identified. This technique provides a novel catalyst-free pathway for the synthesis of cyclic dipeptides.