Effect of water and high pressure on valyl-alanine and alanyl-valine dipeptides cyclization in solid-state

Cyclization of dipeptides in the solid state by heating is a cheap and effective way to obtain 2.5-diketopiperazine derivatives, which are of interest for various technologies and medicine. Solid-state cyclization is an autocatalytic reaction where water released during the reaction acts as a catalyst, but experimental confirmation of this mechanism is lacking due to the rapid evaporation of reaction water at high temperatures. In this study, we investigated the solid-state reaction of L -valyl- L -alanine (Val-Ala) and L -alanyl- L -valine (Ala-Val) dipeptides for the first time using closed systems to prevent water loss, and determined the kinetic parameters of Val-Ala cyclization compared to those previously calculated for Ala-Val. The influence of the molecular structure of Val-Ala and Ala-Val dipeptides and high pressure on enantiopurity has been demonstrated for the reaction product.