Crystalline and Amorphous Phase of Glycyl-Glycine Dipeptide: Thermal Properties and Reactivity

Cyclic dipeptides, derivatives of 2,5-diketopiperazines, possessing a wide spectrum of biological activity and the ability to self-assemble are of interest for medicine and various technologies. Therefore, the development of methods for their preparation is a topical issue. Synthesis of cyclic dipeptides from their linear analogs in the solid state upon heating is a simple, effective, and atom-economical method. However, for widespread use of this method, the problems associated with a decrease in the yield of a product due to its thermal destruction, epimerization, and sublimation should be solved. One of the ways to increase the yield of the reaction product may be the development of methods for reducing the reaction temperature. In this work, the possibility of obtaining cyclic dipeptide cyclo(GlyGly) from linear GlyGly in the solid state using its amorphous phase instead of the crystalline phase was studied. A method for obtaining the amorphous phase of GlyGly was developed; its thermal properties were studied, and a kinetic analysis of the cyclization reaction was carried out. The effect of the initial dipeptide phase on the yield of the cyclic products was estimated.