Synthesis and siderophore activity of albomycin-like peptides derived from N5-acetyl-N5-hydroxy-L-ornithine.
N5-Acetyl-N5-hydroxy-L-ornithine (1), the key constituent of several microbial siderophores, has been synthesized in 23% yield overall from N-Cbz-L-glutamic acid 1-tert-butyl ester (6) derived from L-glutamic acid. Reduction of 6 to 7 and treatment with N-[(trichloroethoxy)carbonyl]-O-benzylhydroxylamine (8), and diethyl azodicarboxylate and triphenylphosphine followed by deprotection produced the protected N5-acetyl-N5-hydroxy-L-ornithine derivatives 11 and 12 in large quantities (10-20 g). Following alpha-amino and alpha-carboxyl deprotections of 11 and 12, EEDQ [2-ethoxy-N-(ethoxycarbonyl)-1,2-dihydroquinoline] mediated peptide coupling and final deprotection provided amino acid 1 and six albomycin-like peptides (20, 23, 25, 28, 35, and 36). The growth-promoting ability of each was evaluated with the siderophore biosynthesis mutant Shigella flexneri SA240 (SA 100 iucD:Tn5). These results indicate that substantial modification of the framework of peptide-based siderophores can be tolerated by microbial iron-transport systems.
Dolence
E K
EK
Department of Chemistry and Biochemistry, University of Notre Dame, Indiana 46556.
Lin
C E
CE
Miller
M J
MJ
Payne
S M
SM
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D055598:Chemical Phenomena; D002621:Chemistry; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D005291:Ferrichrome / Q000031:analogs & derivatives / Q000737:chemistry; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009952:Ornithine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines; D012763:Shigella flexneri / Q000187:drug effects / Q000254:growth & development; D017262:Siderophores
D000900:Anti-Bacterial Agents; D007502:Iron Chelating Agents; D011804:Quinolines; D017262:Siderophores; D005291:Ferrichrome; C029642:delta-N-acetyl-delta-N-hydroxy-L-ornithine; C015657:albomycin; C000470:EEDQ; D007501:Iron; D009952:Ornithine