Si-Linked Glycomimetics through a Stereoselective Silicon Transfer and Anion Addition
Santosh V. Shelar, Timothy M. E. Davis, N.E. Ryan, K. FISCH, Maciej A. Walczak
Abstract
We report a synthesis of silicon-linked glycomimetics, demonstrating unique structural properties and metabolic stability due to the inertness of the C–Si bond. Our method focuses on the stereoselective transfer of silicon and anion addition, revealing that chirality at the silicon atom can be controlled through kinetic resolution. This approach allows for the selective generation of 1,2- cis and 1,2- trans isomers via the manipulation of C2-protected silicon ethers and nucleophilic opening of glycal epoxides. We achieved high selectivity at the anomeric carbon and expanded the scope to include various saccharides and substituted silanes. Our findings indicate that silicon transfer occurs intramolecularly and is influenced by the nature of the counterion and reaction conditions. Additionally, chiral silanes produced through our method hold promise for medicinal chemistry applications, addressing significant gaps in the synthesis and utility of glycomimetics. This work opens new avenues for the development of bioactive silicon-based molecules.