INVESTIGADORES
REPETTO Evangelina
congresos y reuniones científicas
Título:
Synthesis of enantiomeric 2,3,4,5-tetrahydroxyalkylpyrrolidines via 1,3-dipolar cycloaddition from sugar-derived precursors
Autor/es:
MARIANA VARDÉ; OSCAR VARELA; EVANGELINA REPETTO
Reunión:
Simposio; 30th International Carbohydrate Symposium; 2022
Institución organizadora:
ICS
Resumen:
Design and synthesis of glycomimetics has become, in the last years, an interesting approach for the development of new drugs. Iminosugars, widely distributed in nature, are the best developed and major class of sugar mimetics described to date. For these reasons, we center our attention in the synthesis of quiral polyhydroxylated pyrrolidines which could be evaluated as glycosidase inhibitors. These enzymes display an important role in several biological processes; therefore, their inhibition constitutes a good strategy for the development of new therapeutics to treat diverse diseases. In addition, glycomimetics are useful to study biological processes that involve carbohydrates. We have employed the 1,3-dipolar cycloaddition of azomethine ylides and sugar enones derived from pentoses, as a key step in the synthesis of substituted pyrrolidines. Due to the strict diastereocontrol exerted by the stereocenter of the enone, enantiomeric adducts were obtained. Now, we report the 1,3-dipolar cycloaddition of the sugar enone with azomethine ylides. These intermediates were generated from esters of imines derived from 2,2-dimethoxyacetaldehyde and amino acids (glycine or alanine) or those synthesized from aldonolactones. In the latter case, the cycloadducts were entirely based on carbohydrate precursors. Selected cycloadducts were subjected to a sequence of reduction and hydrolysis reactions to afford enantiomeric 2,3,4,5-tetrahydroxyalkylpyrrolidines.