Synthesis and antimicrobial activities of 4-purpuromycin derivatives.
Purpuromycin (1) is a natural antibiotic with a broad spectrum of activity encompassing bacteria, fungi and protozoa. A new series of derivatives of 1 was prepared by the modification or replacement of the C-4 hydroxyl group. The physico-chemical characteristics and the in vitro antimicrobial activity of these new semisynthetic purpuromycin derivatives are reported. Attachment of a variety of bulky groups to the C-4 hydroxyl group as well as acylation or mesylation of 1 gave derivatives with significantly reduced antifungal activity, while the antimicrobial activity of these derivatives against Gram-positive and Gram-negative bacteria was only slightly decreased. All compounds were inactive against Escherichia coli. The C-4 epimers showed different in vitro activity as compared with those having the natural configuration, particularly against fungi.
Trani
A
A
Centro Ricerche Lepetit, Gerenzano VA, Italy.
Dallanoce
C
C
Ferrari
P
P
Goldstein
B
B
Ripamonti
F
F
Ciabatti
R
R
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005658:Fungi / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000494:pharmacology; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D009285:Naphthoquinones; C009115:purpuromycin