Collect. Czech. Chem. Commun. 2006, 71, 978-990

Microwave-Assisted Synthesis of Fluoroquinolones and Their Nucleosides as Inhibitors of HIV Integrase

Martina M. Adamsa, Jan W. Batsa, Nadja V. Nikolausa, Myriam Witvrouwb, Zeger Debyserb and Joachim W. Engelsa,*

a Institute for Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe-University, Marie-Curie-Str. 11, 60439 Frankfurt am Main, Germany
b Molecular Medicine, Katholieke Universiteit Leuven and IRC Kulak, Kapucijnenvoer 33, B-3000 Leuven, Flanders, Belgium


Six fluoroquinolone ribonucleosides were synthesized by using microwave irradiation starting from fluoroanilines. In most cases the microwave application proved superior in time and yield, especially the one step decarboxylation of the carboxyquinolone esters 3a-3c and the Vorbrüggen glycosylation. The former led to the new type of fluoroquinolone ribosides 8a-8c. Compound 8c in the crystal structure showed C3'-endo and anti conformation. The nucleosides were examined, but found inactive against the replication of HIV-1(IIIB) in cell culture, while they were toxic for the cells at a 50% cytotoxic concentration ranging from 31 to >125 μg/ml. But measurements of the inhibitory effects against HIV-1 integrase enzymatic activity showed an interesting activity for compound 8c.

Keywords: Nucleosides; Microwaves; Fluoroquinolones; Glycosidation; Decarboxylation; Anti-HIV activity; HIV integrase; Antivirals.

References: 27 live references.