Synthesis and biological profile of a novel 4-C-branched pyrrolidine-containing iminosugar

A novel 4-C-branched sugar mimetic based on a 1,4-dideoxy-1,4-imino-d-lyxitol (DIL) scaffold was designed and synthesised. Its construction features an early-stage introduction of the side chain via an OCM reaction followed by an alkylative cyclisation, providing the desired heterocyclic system. The subsequent interconversion of functional groups accompanied by the selective deprotection protocol allowed the tetrahydrofuran ring to be cleaved. Cell viability experiments revealed a cytotoxic effect of the target compound comparable to that of cisplatin on the A2058 and MCF-7 cancer cell lines. Moreover, 4-C-tridecyl-DIL proved to be moderately active against Jurkat and HeLa cells (IC₅₀ = 20.58 μM and 22.7 μM, respectively). In addition, docking studies identified the binding modes of this novel pyrrolidine-based iminosugar to human β-glucocerebrosidase.