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

摘要

Asmall 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 R-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.