Solid-phase synthesis of highly diverse purine-hydroxyquinolinone bisheterocycles.
Solid-phase synthesis of bisheterocyclic compounds that contain purine and the 3-hydroxyquinolin-4(1H)-one skeleton connected with an aliphatic spacer of a different length/structure is described. The reaction sequence started from the primary amines immobilized on aminomethylated polystyrene resin equipped with an acid-labile linker (4-(4-formyl-3-methoxyphenoxy)butyric acid). After the arylation of amines with 2,6-dichloropurine via its C(6), purine N(9) was alkylated and subsequently the chlorine at purine C(2) was substituted with aliphatic diamines. The resulting terminal amino group was used as the starting point for the synthesis of 3-hydroxyquinolin-4(1H)-one precursors based on the acylation with 3-amino-4-(methoxycarbonyl)benzoic acid followed by the saponification of the methyl ester and esterification of the resulting carboxylic acid with various haloketones. The intermediates were cleaved from the resin, and their cyclization to the target purine-hydroxyquinolinone bisheterocycles was accomplished by heating in acetic or trifluoroacetic acid.
Vanková
Barbora
B
Department of Organic Chemistry, Faculty of Science, Institute of Molecular and Translational Medicine, University of Palacký, 771 46 Olomouc, Czech Republic.
Hlavác
Jan
J
Soural
Miroslav
M
D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry; D052616:Solid Phase Extraction / Q000379:methods*
D006571:Heterocyclic Compounds; D011687:Purines; D015363:Quinolones