The death of dopaminergic neurons is a major pathological hallmark of Parkinson’s disease (PD). An elevated iron concentration within the substantia nigra of the PD brain catalyses this neuronal death though hydroxyl radical-derived oxidative damage. Removal of this excess iron from the PD brain provides a potential therapeutic strategy. Desferrioxamine B (DFOB) is a high affinity iron(III) chelator used clinically to manage iron overload disease. Although DFOB is highly hydrophilic, adamantyl-based semi-synthetic derivatives of DFOB have been designed with improved lipid solubility to enable blood-brain barrier (BBB) and cell membrane penetration1 . In in vitro PD models, these compounds displayed 65-fold greater performance over native DFOB2 . This project aimed to increase diversity within this group of potential PD therapeutics using an innovative semi-synthetic strategy. Whereas the first generation compounds were unidirectional, these second-generation compounds are bidirectional, allowing greater control of physicochemical properties. Using solution-phase peptide coupling reactions, DFOB was initially bifurcated to allow two sites for chemical attachment. The promising adamantyl derivatives were conserved on one arm, while a range of alternative ancillary fragments can be appended to the second. Conjugation of PEGylated reagents of different monomer lengths, vitamin E and lipoic acid derivatives, and adamantyl- and 8-hydroxyquinoline-based ancillary groups are expected to allow tuning of plasma residence time, the introduction of additional anti-oxidant properties, and the imparting BBB carrier properties, respectively. This project has enabled a deeper understanding of the boundaries of DFOB semi-synthesis, and has designed an operating framework for the preparation of bifurcated adamantyl-based DFOB derivatives.