Banca de QUALIFICAÇÃO: MARIANA TEIXEIRA CORDEIRO

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : MARIANA TEIXEIRA CORDEIRO
DATE: 27/03/2026
TIME: 08:00
LOCAL: https://meet.google.com/ajt-dggf-ngk
TITLE:

APPLICATION OF N-HALOSUCCINIMIDES AND TRICHLOROISOCYANURIC ACID IN THE PREPARATION OF GENINS AND THE SYNTHESIS OF DIGOXIGENIN DERIVATIVES

KEY WORDS:

Hydrolysis; N-halosuccinimides; Trichloroisocyanuric acid; Digoxigenin; Green Chemistry.

PAGES: 44
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SPECIALTY: Síntese Orgânica
SUMMARY:

Cardiotonic steroids constitute a class of natural metabolites isolated from different organisms, including plant and animal sources. These compounds exert their main pharmacological action through inhibition of the Na⁺,K⁺-ATPase enzyme, leading to increased cardiac muscle contractility. In addition to their positive inotropic effect, they also modulate several intracellular signaling pathways. Genins, the aglycone molecules derived from these steroids, are of significant pharmacological interest because they retain the steroidal nucleus and the unsaturated lactone ring, which are essential pharmacophores for interaction with Na⁺,K⁺-ATPase. In order to develop a simpler and more environmentally friendly method for genin synthesis in accordance with Green Chemistry principles, N-halosuccinimides and trichloroisocyanuric acid (TCCA) were employed as catalysts in the hydrolysis of digoxin, affording yields higher than 96% when ethanol and water were used as solvents. Under optimized conditions, TCCA provided a 99% yield and was also successfully applied to the hydrolysis of digitoxin, giving an equivalent yield for this cardenolide. To obtain derivatives from digoxigenin, oxidation and reduction reactions were carried out. Oxidation at the C-3 carbon led to formation of the corresponding ketone in 70% yield, whereas stereochemical modification at the same center resulted in the formation of the diastereoisomer 3R-digoxigenin. Additionally, a novel molecule was synthesized through condensation between benzaldehyde and the genin, with a 50% yield. This compound, as well as the ketone and the obtained genins, was characterized by proton and carbon-13 nuclear magnetic resonance spectroscopy (¹H and ¹³C NMR), electrospray ionization mass spectrometry (ESI-MS), and infrared spectroscopy (IR). As future perspectives, the synthesis and characterization of the corresponding digitoxigenin ketone are highlighted, as well as the complete structural characterization of 3R-digoxigenin. Further oxidation of the lactone ring of the novel molecule is also proposed in order to obtain a compound structurally analogous to bufadienolides.

BANKING MEMBERS:
Externo ao Programa - 1421228 - LUCAS RAPOSO CARVALHO
Presidente - 3125781 - RAFAEL MAFRA DE PAULA DIAS