Synthesis and Characterizationof 4-Thiobutyl-triphenylphosphonium -pantetheine, aPantetheine Derivative

Pantetheine, a low molecular weight thiol, has been found to ameliorate symptoms in various disease models but specifically in Pantothenate Kinase -Associated Neurodegeneration (PKAN). Pantetheine is usually administered in its disulfide form (i.e. pantethine) since pantethine is commercially available and is reduced to pantetheine in biological systems. The applicability and efficacy of pantethine (therefore also pantetheine) as a clinical therapeutic however is hampered since both forms can be degraded by pantetheinases present in the body.Here, we report the synthesis of a masked form of pantetheine, namely4-thiobutyltriphenylphosphonium-pantetheine (TBTPpantetheine), following our hypothesis that this pantetheine -derivative might be more stable in thepresence of pantetheinases than pantetheine itself. Higher stability would enhance transport into the cytoplasm where TBTP -pantetheine is metabolized into