Estudo químico dos frutos e da biossíntese dos alcaloides piperidínicos de Senna spectabilis

Abstract

Senna spectabilis (Fabaceae) is an important species found throughout the Brazilian territory, rich in chemical diversity, with piperidine alkaloids as its major constituents. These alkaloids exhibit action on the central nervous system by inhibiting acetylcholinesterase, an enzyme linked to cognitive processes, whose deficiency is associated with Alzheimer's disease. This array of active molecules positions plants as promising protagonists in the discovery and development of new medicines. However, due to the escalating environmental degradation compromised the production of these metabolites. These facts have motivated us to conduct a chemical study of S. spectabilis fruits, aiming to isolate new compounds, as well as investigate the biosynthesis of piperidine alkaloids for a better understanding of the pathways responsible for producing these metabolites. Initially, the ethanolic extract of green fruits was prepared and subjected to liquid-liquid extraction with solvents of increasing polarity. The alkaloid fraction (CH2Cl2) was subjected to column chromatography resulting in the isolation of the alkaloids (– )-cassine (8) (12.0 mg) and (–)-spectaline (14) (11.4 mg), along with a mixture of homologs 3-O-feruloylcassine (26) and 3-O-feruloylspectaline (27) (14.4 mg). The isolated compounds structures were elucidated through spectroscopic techniques (IES-MS) and spectrometric methods (NMR). For the elucidation of biosynthetic pathways, seeds were cultivated in soil to confirm the active metabolism of the species, as evidenced by GC-MS analyses demonstrating the presence of alkaloid (8) in the chloroform fraction, with its substantial increase over the growth period. In vitro cultivation conditions of S. spectabilis seeds were optimized, being Wood Plant (WP) culture medium, which presented the best results. In growth experiments with the addition of 1-13C-D-glucose (54 days), a pattern of incorporation into piperidine alkaloids was observed in the chloroform fraction of the aerial parts (EC-PA), analyzed via GC-MS. From this fraction, alkaloid (8) (0.5 mg) was isolated. The analysis of HPLC-IES-MS and GC-MS results suggests that the formation of these alkaloids in S. spectabilis originates from the acetate pathway.