Síntese de derivados de cis-β-tio-α-aminoácidos catalisada por bis-l-prolinato de zinco (II)

Abstract

Matrix metalloproteinases have been widely studied as participating in a large number of physiological processes in the human metabolism, as in pathological processes in the joint destruction in cases of rheumatoid arthritis, osteoarthritis, abdominal aortic aneurysm, myocardial infarction and cancer. There is a growing interest in the development of research of biological inhibitors of MMPs that can be successfully used in biological processes. Some MMPs inhibitors and MMP-13, MMP-2-9, marimastat, prinomastat, BMS-275291 and BAY 12-9566 are derived from β-substituted-α-amino compounds and are found as chiral ligands, catalysts, products pharmaceuticals, peptides. However, for some time the synthesis of β-substituted-α-amino acid compounds has not been explored, and due to its countless utility, this paper proposes the synthesis of these compounds. To obtain β-substituted-α-amino, oxazolones rings are exploited. With the aim of developing a simple synthesis process and "green" β-tio-α-amino acid insertion proposed a heterogeneous chiral catalyst for these types of reactions, proposed the use of bis - (N, O prolinate) zinc (II) or simply Zn[(L)-Pro]2. The use of ethanol as solvent and Zn[(L)-Pro]2 as catalyst were essential for this methodology, the effect of the catalyst was investigated and showed that high diastereomeric excess was achieved when using 20 mol% of the catalyst. The products were obtained in reaction 2 hours and readily purified by recrystallization from ethanol. A series of compounds was synthesized obtained in good to excellent yields (up to 100%) with excellent diastereoselectivity, especially for the cis-compound, depending on the variations of temperature (0° C, 80 °C and room temperature) by ultrasound device. It was concomitantly investigated the influence of temperature on the reaction yield and the diastereomeric excess, depending on the temperature variation (0°C, 80°C and room temperature) by ultrasound device, resulting in excellent diastereoisomeric excess for the cis isomer 0°C in temperature and the trans isomers best diastereomeric excesses to 80°C. Compounds obtained were characterized via IR, 1H NMR, 13C proving that this methodology have been possible to obtain the desired compounds.