Síntese de tiazolidin-4-onas e tiazinan-4-onas análogas da rosiglitazona e síntese de tiazinan-4-onas derivadas da 1-(2aminoetil)pirrolidina

Abstract

The present work reports the synthesis of thiazolidin-4-ones and thiazinan-4ones

analogous to the antidiabetic drug rosiglitazone. Also, was synthesized the thiazinan-4-ones from 1-(2-aminoethyl)pyrrolidine. Synthesis of rosiglitazone analogs involves the structural modification of glitazone ring by the thiazolidin-4-ones and thiazinan-4-ones ring. The analogous compounds were performed in three reaction steps. The first and second steps occurred by nucleophilic aromatic substitution reaction using the microwave methodology for the formation of 4-(2-(methyl(pyridin-2yl)amino)ethoxy)benzaldehyde.

After, the third step was performed for the synthesis of thiazolidin-4-ones and thiazinan-4-ones involves the reaction of addition to carbonyl followed by cyclocondensation via multicomponent "one-pot", through the conventional thermal heating methodology. The thiazolidin-4-ones synthesis protocol was similar to thiazolidin-4-ones encompassing three components (primary amine, drug benzaldehyde and mercaptocarboxylic acid). Therefore, the synthesis of thiazinan-4-ones derived from 1-(2-aminoethyl)pyrrolidine was carried out via a onepot

multicomponent reaction using different benzaldehydes and the conventional thermal heating methodology. All compounds obtained were identified by gas chromatography coupled to the mass spectrometer (GC/MS), and by C nuclear magnetic resonance (NMR). Furthermore, some compounds were also characterized by: 2D NMR (COSY, HSQC, HMBC), high resolution mass spectrometry (EMAR) and X-ray diffraction crystallography. The thiazinan-4-ones heterocycles derivatives 1-(2-aminoethyl)pyrrolidine were also tested for biological assays in front of acetylcholinesterase inhibition (AChE) activity and cytotoxicity study by cell viability test against cortical astrocytes.