Solution versus Fluorous versus Solid-Phase Synthesis of 2,5-Disubstituted 1,3-Azoles. Preliminary Antibacterial Activity Studies

A small library of compounds with an oxa(thia)zole scaffold and structural diversity in both positions 2 and 5 has been synthesized. Double acylation of a protected glycine affords intermediate α-amido-β-ketoesters, which in turn can be dehydrated to afford 1,3-oxazoles or reacted with Lawesson’s reagent to furnish 1,3-thiazoles. This procedure was designed with its adaptation to fluorous techniques in mind. Thus, when a protected glycine with a fluorous tag in the ester moiety is used as a starting material, the synthesis can be easily completed without column chromatography purification of intermediate compounds with good to excellent yields, thus affording a suitable entry to the preparation of small libraries of these bioactive compounds. The prepared oxa(thia)zoles were assayed for their antibacterial activity, and several of them were active against Staphylococcus aureus. Fil: Sanz Cervera, Juan F.. Universidad de Valencia; España Fil: Blasco, Raül. Universidad de Valencia; España Fil: Piera, Julio. Universidad de Valencia; España Fil: Cynamon, Michael. SUNY Upstate Medical University; Estados Unidos Fil: Ibáñez, Ignacio. Universidad de Valencia; España Fil: Murguia, Marcelo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Fustero, Santos. Universidad de Valencia; España