N-Hydroxy ornithine

Figure 11. Structure of the ferrichromes. The basic structural feature is a cyclic hexapeptide with the three hydroxamic acid linkages provided by a tripeptide of SN-acyl- N-hydroxy- -ornithine. The A-cis coordination iser is shown in each...

The first synthesis of a siderophore was the preparation of ferrioxamine B over 20 years ago in order to confirm the chemical structure of this natural product67). Synthesis of the other hydroxamate containing siderophores has as a central problem preparation of the constituent to-N-hydroxy amino acid in an optically pure form. The most important such subunit in hydroxamate siderophores is Ns-hydroxy ornithine. This is a chiral building block of the diketopiperazine-containing siderophores (rhodo-torulic acid 68), dimerum acid 69), coprogen 70) and coprogen B 69>), the cyclic hexa-peptides of the ferrichrome family27), the fusarinines 71 -73) and the antibiotic ferri-chrome derivatives albomycines Sl5 S2 and e 61-62). 

Figure 3. Effect of pentachlorophenol on the N-hydroxy-2-acetyl-amlnofluorene-induced increase in ornithine decarboxylase (ODC) activity in rat liver. N-hydroxy-2AAF or 2AAF was administered i.p. <94 and 63 Jmol/kg i.p. respectively). One hour prior to N-hydroxy-2AAF, pentachlorophenol <40 ymol/kg) was given. ODC was measured in liver cytosol. (Reproduced with permission from Ref. 23. Copyright 1984, Marcel Dekker.)...

The ferrichromes comprise one large family of hydroxamate siderophores (Figure 1 (a)) and were isolated from low-iron cultures of many fungi. With few exceptions, ferrichromes possess cyclic hexapeptide backbones in which one tripeptide is linked to a second tripeptide of Al -acyl-N -hydroxy-L-ornithine. Linear derivatives of the latter tripeptide form backbones of various antibiotics, termed albomycines. 

Lee, B.H., G.J. Gerfen, and M.J. Miller Constituents of Microbial Iron Chelators. Alternate Syntheses of 6-N-Hydroxy-a-ornithine Derivatives and Applications to the Synthesis of Rhodotorulic Acid. J. Organ. Chem. (USA) 49, 2418 (1984). 

S.P. solid-phase technique L.P. liquid-phase technique OPTcp pentachlorophenyl ester TEEP tetraethyl pyrophosphit OTCp trichlorophenyl ester ONp p-nitrophenyl ester ONSu N-hydroxysuccinimido ester OPFp pentafluorophenyl ester OQu 8-hydroxyquinyl ester OPy 3-hydroxy-pyridyl ester ODnp 2,4-dinitrophenyl ester DCC dicyclohexylcarbodiimide HOBn 3-hydroxy-4-oxo-3,4-dihydro-l,2,3-benzotriazin Opi JV-hy-droxypiperidine EEDQ 2-ethoxy-l-ethoxycarbonyl-l,2-dihydroquinoline Tos p-toluenesulfonyl PTC propanetricarboxylic acid OBu tm-butyl ester Nva norvaline Aha aminohexanoic acid Om ornithine... 

Deferriferrichrome is an amorphous, almost colorless solid. Hydrolysis in 6N HC1 affords glycine (3 moles) and N S-hydroxy-L-ornithine (3 moles). Reductive hydrolysis in 50% HI gives L-ornithine (3 moles). Oxidation with NaI04 yields acetic acid (3 moles). 

D-valine, A-methyl-L-valine, L-norvaline, L-y-formylmethylnorvaline L-ornithine, n-ornithine, IV-hydroxy-L-ornithine L-Ianthionine, 3-methyl-L-lanthionine... 

Albomycins. Iron-containing antibiotics belonging to the sideromycins from various streptomycetes strains (e. g. Streptomyces subtropicus). The iron-free form is a peptide composed of 3 molecules Af -acetyl-Af -hydroxy-L-ornithine, I mol. L-serine, and an unusual amino acid, with a variable pyrimidine part and an N-glycosidically bound thiofuranose. The iron(lll) complexes of the hydroxamate siderophores have a red color and are highly active against bacteria. 

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