Siderophore Building Block: New Hydroxamate-Ornithine for Fmoc/tBu SPPS

Published on 03/12/2015

N^δ-hydroxy-N^δ-acetyl-ornithine, an important constituent of many siderophores, is now available for your convenience as N^α-Fmoc-N^δ-(acetyl)-N^δ-(benzoyloxy)-ornithine building block which can be used in standard Fmoc/tBu SPPS and permits facile on-resin N^δ-deprotection.

Ornithine is a pivotal amino acid in microbial cell metabolism. Among other things, bacteria utilize ornithine for the synthesis of peptidoglycan and lipids. Moreover, Orn is an important constituent of certain antibiotics, such as the highly bactericidal Daptomycin.

Siderophore Building Block: New Hydroxamate-Ornithine for Fmoc/tBu SPPS

The hydroxamate-ornithine derivative N^δ-hydroxy-N^δ-acetyl-ornithine is a bidentate ligand that is found in many siderophores. Siderophores are small peptides and other biomolecules that form stable hexadentate octahedral complexes with Fe³⁺ and other metal ions. They are used by microorganisms during iron depletion in order to scavenge iron from the environment. Siderophores are taken up by specific microbial receptors and transport systems, a property that can be exploited to deliver antibiotics via Siderophore-Drug-Conjugates. Since it bypasses the bacterium’s defences, this method is aptly termed the “Trojan Horse” strategy.

Ferrichrome binding Fe (III); Quelle: Wikipedia

N^α-Fmoc-N^δ-(acetyl)-N^δ-(benzoyloxy)-ornithine is now available for your convenience. It is suitable for SPPS using standard Fmoc/tBu chemistry. Moreover, this novel building block permits on-resin N^δ-deprotection by debenzoylation using 1 M LiOH in THF/MeOH. These properties allow for rapid and convenient incorporation of N^δ-hydroxy-N^δ-acetyl-ornithine for the synthesis of novel target peptides.

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