Síntese de vinilamidas utilizando [Ce(L-Pro)2]2Oxa como catalisador heterogêneo

Abstract

Peptides are present in a series of physiological and pathological processes in the body, such as uncontrolled cell division, which could lead to malignant and/or immunological diseases. Vinylamides are known to be effective against a series of disorders, such as malaria, inflammatory, respiratory, and viral diseases. Due to their importance, vinylamides have been the subject of much research in the field of biology. Studies have started the importance of this class of compounds in the synthesis of peptides, antimicrobial, antitumor compounds, protein biosensors, HIV inhibitors, and important medicines. However, such methods present several disadvantages, especially a loss of the stereochemistry present in the start compound, due of the racemization involving of Brønsted acids used in the process as catalysts. Thus, in this work, vinylamides are synthesized from the reaction involving several anilines and azlactones with defined stereochemistry in the presence of the heterogeneous catalyst [Ce(LPro) 2]2Ox. Three parameters were analyzed in the reaction, they are: (1) the percentage amount of catalyst, (2) the best reaction time and (3) the choice of the ideal solvent. For the synthesis of the vinylamides was used 10% mol of the catalyst [Ce(L-Pro)2]2Ox and during the optimization of the reaction mixture it was observed that in four hours the azalactone was completely consumed. After these two parameters were identified, the effect of the solvent on the reaction was verified, and it can be observed that the reaction has a higher affinity with solvents of high polarity, therefore ethanol is chosen, as is an environmentally-friend solvent. The twenty-two products are purified via column chromatography (Hexane:Ethyl Acetate (9:1)/CHCl3/Ethanol) and are characterized by spectroscopic techniques Infrared (IR) for the standard compound, 1H e 13C NMR for the standard compound and all their derivatives. Subsequently, the possibility of re-use of the cerium catalyst in the other reaction cycles was verified and the realization of the synthesis in scale up, also. Finally, through reactions datas obtained and theoretical calculations, it was possible to reach a conclusion of a totally plausible reaction mechanism for the synthesis of vinylamides.