The Gram-negative bacterium Pseudomonas aeruginosa produces a family of peptide siderophores called pyoverdines that play a vital role in the mechanisms by which it acquires iron from the environment. A key component of various pyoverdines is the presence of one or more copies of L-δ-N-formyl-δ-N-hydroxyornithine (fOHOrn) as an iron-binding residue. In this study, we have developed an improved preparation of a derivative of fOHOrn that is suitable for use in solid-phase peptide synthesis, incorporating a novel N-oxidation protocol and a mild final deprotection with HCl/hexafluoroisopropanol (HFIP) that circumvents the unexpected deformylation of the fOHOrn side chain under acidic conditions. We have also devised a synthesis of the cyclic peptide component of pyoverdine D exploiting a selective side-chain deprotection strategy with HCl/HFIP that allows the application of readily available amino acids with standard tert-butyl side-chain protection and which facilitates the cyclisation step. These innovations open the way towards the convergent preparation of various pyoverdines and also other natural products that contain fOHOrn residues.
Zhang et al. (Sat,) studied this question.