Synthesis and biological evaluation of 4,4-dimethyl-5,5-di(1-methylethyl)-2,3,4,5-tetrahydro-1 H-dipyrrolo[3,4-d:2,1-f][1,2]azasiline-1,3-dione and other pyrrolediones as new antibacterial active agents.
The UV-light induced photosubstitution of 3,4-dibromo-2,5-dihydro-1H-2,5-pyrroledione (2) [1] with pyrrole derivatives leads to 3-mono- and 3,4-disubstituted pyrrolediones depending on the starting material. These pyrrole homologues of arcyriarubin A (1) are further processed by nucleophilic substitution of the remaining bromine substitutent with pyrrolidine. Cleavage of the protecting group affords the free pyrrole substituents. By UV-light irradiation the azasiline-system (6) is accessible, and its structure was established by X-ray methods. The in vitro antibacterial activity of the pyrrolediones was evaluated, and a strong activity of the compounds 4, 7, 8 and 12 against the methicillin- and ciprofloxacin-resistant bacterium Staphylococcus aureus 134/94 was established.
Mahboobi
S
S
Faculty of Chemistry and Pharmacy, University Regensburg, Germany.
Popp
A
A
Fleck
W F
WF
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects; D018360:Crystallography, X-Ray; D007093:Imidazoles / Q000138:chemical synthesis* / Q000633:toxicity; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects
C402109:4,4-dimethyl-5,5-di(1-methylethyl)-2,3,4,5-tetrahydro-1H-dipyrrolo(3,4-d-2,1-f)(1,2)azasiline-1,3-dione; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000935:Antifungal Agents; D007093:Imidazoles; D011758:Pyrroles