Obtenção de álcoois e ésteres quirais utilizando lipases e resolução cinética enzimática da ketamina e análogos

Abstract

In this work the enantiomerically pure compounds were obtained using lipases. Chapter 1 was dedicated to the study of obtaining chiral alcohols and esters from acetophenones and derivates using the commercial CAL-B for comparison with the recombinant enzyme of Bacillus coagulans. For this, the esters rac-3a-k were initially hydrolyzed with CAL-B, presenting good results of ees (>99%), eep (>99%), C (50%) e E (>200), With the exception ofrac-3k (2,5dimethylphenyl) ethyl acetate, which showed low conversion values and e.e.s. The reaction with the recombinant carboxylesterase was done only with the substrate rac-3a used as model, however it did not present activity. While attempting to optimize expression conditions and enzymatic activity, the study of kinetic resolution via acetylation using Pseudomonas fluorescens lipase in its forms: free, commercially immobilized and immobilized on magnetic nanoparticles using the substrates rac-2a, rac-2b and rac-2f. The results showed that the kinetic resolution for these substrates catalyzed by P. fluorescens immobilized on magnetic nanoparticles was highly enantioselective with E> 200 values. In Chapter 2, the enzymatic kinetic resolution of ketamine and the analogue was studied using different commercial lipases. At first, enzymatic kinetic resolution of ketamine was achieved by hydrolysis using the carbamate of ketamine rac-5 with 8 commercial lipases, and no activity was observed in any of the enzymes studied. Subsequently, enzymatic kinetic resolution of ketamine via carbonation was performed using the CAL-B and TLL enzymes, which also did not present satisfactory results. Finally, enzymatic kinetic resolution was performed via hydrolysis of a ketamine analog rac-8. The results obtained for this reaction were also not satisfactory, and no reports were found in the literature for the synthesis or enzymatic kinetic resolution of this compound. The negative results may be related to the steric hindrance that the Cl atom and the benzene ring can generate, making it difficult to fit the enzyme-substrate and consequently preventing the reaction.