Synthesis of Enantiomeric Polyhydroxyalkylpyrrolidines from 1,3-Dipolar Cycloadducts. Evaluation as Inhibitors of a β-Galactofuranosidase.
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-(menthyloxy)hexahydropyrano[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; in particular, 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 β-galactofuranosidase from Penicillium fellutanum. The compounds showed practically no inhibitory activity for concentration of pyrrolidines in the range of 0.1-1.6 mM.
CIHIDECAR-CONICET-UBA, Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires , Pabellón 2, Ciudad Universitaria, 1428 Buenos Aires, Argentina.
Guillermo A
GA
Oliveira Udry
CIHIDECAR-CONICET-UBA, Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires , Pabellón 2, Ciudad Universitaria, 1428 Buenos Aires, Argentina.
Evangelina
E
Repetto
Departamento Física de la Materia Condensada, GAIyANN-CAC-CNEA y ECyT-UNSAM , Av. Gral. Paz 1499, San Martín, 1650 Buenos Aires, Argentina.
Daniel R
DR
Vega
CIHIDECAR-CONICET-UBA, Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires , Pabellón 2, Ciudad Universitaria, 1428 Buenos Aires, Argentina.
Oscar
O
Varela
D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D061565:Cycloaddition Reaction; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D006868:Hydrolysis; D008958:Models, Molecular; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D010407:Penicillium / Q000187:drug effects / Q000201:enzymology; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013237:Stereoisomerism
D001643:Bridged Bicyclo Compounds; D004791:Enzyme Inhibitors; D011759:Pyrrolidines; D006026:Glycoside Hydrolases; C023112:exo-beta-D-galactofuranosidase