Resolução cinética enzimática de precursores da fenilalanina obtidos via catálise de transferência de fase (CTF).

Abstract

In this work reactions of C-alkylation were carried out via Phase Transfer Catalysis (PTC) in order to obtain precursors of amino acids and them to perform enzymatic kinetic resolution. The reactions of C-alkylation occurred at 70 °C, several phase transfer agents were tested, and the most promising was the benzyltributylammonium chloride (CBTBA). The reaction were performed using 3 mmol of ethyl cianoacetoamidoacetate, 3 mmol of potassium carbonate, 6 mmol of alkylating agent, benzylchloride. After purification of the product, a reaction of total hydrolysis was carried out with subsequent protection of amino and carboxyl groups resulting in three different compounds rac-33 rac-34 and rac-35. The enzymatic kinetic resolution of rac-33 via interesterification with butyl butyrate (PrCO2Bu) was initially tested with different lipases (Candida antarctica Lipase B and it’s isoenzyme, Lipase Candida antarctica Lipase A, ACYLASE I obtained from Aspergillus melleus, PSL-C I, Lipase from Candida rugosa and Lipozyme RM IM) varying time, temperature and solvent. The Lipozyme RM IM was the only enzyme capable of promoting the reaction of interesterification and with high values of enantioselectivity (E). The best reactions occurred at 55 °C. The resolution of rac-33 at 55 ° C occurred in eight hours and fifteen minutes in system solvent free, with conversion of 50%, eeS>99%, eeP>99% with a high value of enantioselectivity, E > 200 (10633), Scheme 3. The kinetic resolution of allyl 2-acetylamino-3-phenyl-propanoate (rac-35) occurred in four hours and thirty minutes, without any solvent at 55 ° C, resulting in 49% of conversion, eeS>98%, eeP>99% and E > 200 (9278).