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 alpha-amido-beta-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.
Sanz-Cervera
Juan F
JF
Departamento de Química Orgánica, Universidad de Valencia, 46100 Burjassot, Spain. juan.f.sanz@uv.es
Blasco
Raül
R
Piera
Julio
J
Cynamon
Michael
M
Ibáñez
Ignacio
I
Murguía
Marcelo
M
Fustero
Santos
S
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001393:Azoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D008826:Microbial Sensitivity Tests; D015335:Molecular Probes / Q000138:chemical synthesis; D054852:Small Molecule Libraries / Q000138:chemical synthesis*; D012996:Solutions; D013211:Staphylococcus aureus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D001393:Azoles; D015335:Molecular Probes; D054852:Small Molecule Libraries; D012996:Solutions