Preparação e avaliação biológica de complexos lipofílicos de ouro(I) e síntese de ésteres ativos e acilcarbamatos via carbonilação catalisada por paládio

Abstract

Therapeutic gold values are known since ancient China and gold complexes are currently employed in the treatment of rheumatoid arthritis. Other biological properties relative to the complexes of gold(I) have been reported in the literature, such as antitumor activity, antibacterial, antiviral and antifungal. The first part of this thesis describes the synthesis of novel lipophilic complexes of gold(I) containing core 1,3,4-oxadiazol-2-thione or 1,3-thiazolidine-2-thione, and they are constituted by tertiary phosphines, such as triphenylphosphine or triethylphosphine. After characterization using usual analythical methods (NMR 1H, 13C, 31P, IR and HRMS) the biological evaluations were performed in vitro for all complexes of gold(I) and their organic ligands. The cytotoxic results against tumor cells (CT26WT and B16F10) and normal cells (BHK21) show pronounced antitumor activity due to low IC50 values compared to the values obtained for the corresponding ligands and Cisplatin. The antibacterial activity for the complexes of gold(I) against Gram-positive bacteria Staphylococcus aureus and Staphylococcus epidermidis also proved to be satisfactory, since the complexes exhibit low MIC values compared to the results obtained for the ligands and chloramphenicol. The development of catalytic methodologies by transition metals, in particular the use of palladium, has attracted considerable attention in the academia and industry. Thus, the second chapter covers the development of a general method for preparation of active esters via palladium catalyzed alkoxycarbonilation and carbonilative coupling of aryl halides, potassium cyanate, alcohols and carbon monoxide. In both cases the generality of the protocols is confirmed by the diversity and good yields obtained to the scope from different nucleophiles and aromatic and heteroaromatic halides.