ABSTRACT
Novel oxazolidinone antibacterials containing N-hydroxyacetamidine moiety are synthesized with the diversity at C-5 terminus. These compounds have been evaluated against a panel of clinically relevant gram-positive and gram-negative pathogens. Most of the analogs in this series displayed activity superior to Linezolid and in vivo efficacies of selected oxazolidinones are also disclosed herein.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Hydroxamic Acids/chemistry , Oxazolidinones/chemical synthesis , Oxazolidinones/pharmacology , Animals , Anti-Bacterial Agents/chemistry , Disease Models, Animal , Gram-Negative Bacteria/drug effects , Gram-Negative Bacterial Infections/drug therapy , Gram-Positive Bacteria/drug effects , Gram-Positive Bacterial Infections/drug therapy , Mice , Microbial Sensitivity Tests , Molecular Conformation , Oxazolidinones/chemistry , StereoisomerismABSTRACT
In the process development of lovastatin using Aspergillus terreus DRCC 152 in solid state fermentation, we have isolated a new butyrolactone-IV (3) along with the previously reported butyrolactone-I (1) and butyrolactone-II (2) produced under submerged conditions. The structure of compound 3 has been characterized as 3-hydroxy-5-[2-(1-hydroxy-1-methylethyl)-2(R)-2,3-dihydro-benzo[b]furan- 5 ylmethyl]-4-(4-hydroxyphenyl)-5-methoxycarbonyl-(5R)-2,5-dihydro-2 -furanone on the basis of spectroscopic studies. The absolute stereochemistry has been determined by single crystal X-ray diffraction studies. The cytotoxic and antibacterial activities of these compounds were determined.
