Practical Synthesis of Hydroxamate-Derived Siderophore Components by an Indirect Oxidation Method and Syntheses of a DIG−Siderophore Conjugate and a Biotin−Siderophore Conjugate

• Published in: Journal of organic chemistry Vol. 64; no. 20; pp. 7451 - 7458
• Main Authors: Lin, Yun-Ming, Miller, Marvin J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.10.1999; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; ARTIFICIAL SIDEROPHORES; MEDIATED DRUG-DELIVERY; ANTIBACTERIAL ACTIVITY; ANALOGS; CHELATORS; ESCHERICHIA-COLI; L-ORNITHINE; RHODOTORULIC ACID; IRON TRANSPORT CAPABILITIES; MYCOBACTIN
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo990769y

A practical large-scale synthesis of hydroxamate-derived siderophore components (30 and 40) that utilizes an efficient indirect oxidation method is described and applied to the syntheses of nonradioactive labeled siderophores. Oxidation of imines derived from l-ornithine (17) and its tripeptide (19) afforded oxaziridines that were isomerized to stable nitrones (16 and 18). Acid-catalyzed hydrolysis of nitrones provided hydroxylamines that were converted to the desired hydroxamic acids (30 and 40) suitable for constructing siderophore−drug conjugates (2). The entire synthetic sequence required no chromatographic separation. DIG- and biotin-labeled ferrichrome analogues designed to detect and isolate ferrichrome receptors in various microbes were also synthesized.