Abstract:
The lysosomal storage accumulation of neurotoxic molecules named glucoside-cholesteryls (GlcChol) due to mutation in the GBA1 enzyme is proved to be strictly correlated to Parkinson's disease. The literature to date on their pathways and interaction with cellular receptor in biological systems is scarce, and their biosynthesis exploiting suitable organisms unsuccessful.
Our contribution is to develop an optimized strategy for the total synthesis of a derivative of α-GlcChol, functionalized towards subsequent receptor engagement. The target molecule was obtained in eight synthetic steps. The last step, involving the protected saccharide and the dehydroepiandrosterone derivative, was carried in a confined area, because of the potential hazard of the biologically active final product. The reactive alkyne tail of the final compound can be further functionalized through "click" chemistry with proper azide derivatives such as nano-beads, fluorophores and biotin, to enable cellular reception in biological systems.
