Synthesis of enantiomeric polyhydroxyalkylpyrrolidines from 1,3-dipolar cycloadducts. Evaluation as inhibitors of a beta-galactofuranosidase

GUILLERMO A. OLIVEIRA UDRY; EVANGELINA REPETTO; DANIEL R. VEGA; OSCAR VARELA

JOURNAL OF ORGANIC CHEMISTRY

AMER CHEMICAL SOC

Lugar: Washington; Año: 2016 vol. 2016 p. 4179 - 4189

0022-3263

Enantiomeric 2,3,4-tris(hydroxyalkyl)-5-phenylpyrrolidines have been synthesized from the major cycloadducts obtained by the 1,3-dipolar cycloaddition of sugar enones with azomethine ylides derived from natural amino acids. Reduction of the ketone carbonyl group of the cycloadducts, which possess a basic structure of bicyclic 6-menthyloxyhexahydropyrano[4,3-c]pyrrol-7(6H)one, afforded a number of pyrrolidine-based bicyclic systems. A sequence of reactions, which involved hydrolysis of the menthyloxy substituent, reduction, N-protection and degradative oxidation, afforded varied pyrrolidine structures having diverse configurations and patterns of substitution, particularly polyhydroxylated derivatives have been obtained. The unprotected products were isolated as pyrrolidinium trifluoroacetates. Because of the furanose-like nature of the target trihydroxyalkyl pyrrolidines, these molecules have been evaluated as inhibitors of the beta-galactofuranosidase from Penicillium fellutanum. The compounds showed practically no inhibitory activity for concentration of pyrrolidines in the range of 0.1 to 1.6 mM.