N-alpha-(9-Fluorenylmethyloxycarbonyl)-N-delta-acetyl-N-delta-benzoyloxy-L-ornithine

The hydroxamate-ornithine derivative N-delta-hydroxy-N-delta-acetyl-ornithine is a bidentate ligand that is found in many siderophores, a Fe(III)-binding class of biomolecules that can be employed as siderophore-drug-conjugates (“Trojan Horse Strategy”). The N-alpha-Fmoc-N-delta-acetyl-N-delta-benzyloxycarbonyl-L-ornithine building block is suitable for SPPS. Moreover, the N-delta-group can be deprotected on-resin to liberate the native metal-ion-binding N-delta-hydroxy-N-delta-acetyl-motif. Conditions for on-resin N-delta-deprotection: 1 M LiOH in THF/MeOH (1:1) References: Enterobactin-Mediated Delivery of ß-Lactam Antibiotics Enhances Antibacterial Activity against Pathogenic Escherichia coli; T. Zheng and E. M. Nolan; Journal of the American Chemical Society 2014; 136: 9677-9691. doi:10.1021/ja503911p Siderophore-Mediated Cargo Delivery to the Cytoplasm of Escherichia coli and Pseudomonas aeruginosa: Syntheses of Monofunctionalized Enterobactin Scaffolds and Evaluation of Enterobactin-Cargo Conjugate Uptake; T. Zheng, J. L. Bullock and E. M. Nolan; Journal of the American Chemical Society 2012; 134: 18388-18400. doi:10.1021/ja3077268 Exploiting bacterial iron acquisition: siderophore conjugates; C. Ji, R. E. Juarez-Hernandez and M. J. Miller; Future medicinal chemistry 2012; 4: 297-313. doi:10.4155/fmc.11.191 Design and synthesis of a siderophore conjugate as a potent PSMA inhibitor and potential diagnostic agent for prostate cancer; P. Ding, P. Helquist and M. J. Miller; Bioorganic & Medicinal Chemistry 2008; 16: 1648-1657. doi:http://dx.doi.org/10.1016/j.bmc.2007.11.030 Design and synthesis of a novel protected mixed ligand siderophore; P. Ding, C. E. Schous and M. J. Miller; Tetrahedron letters 2008; 49: 2306-2310. doi:10.1016/j.tetlet.2008.02.007