Comparing Chemoenzymatic and Conventional Synthetic Strategies to Wall Teichoic Acid Peptidoglycan Fragments

In the cell wall of Gram‐positive bacteria, wall teichoic acid (WTA) is an abundant and conserved virulence factor. WTAs are especially relevant to Methicillin‐resistant Staphylococcus aureus. Tremendous synthetic efforts have permitted investigations of the terminal end of this glycopolymer. However, the peptidoglycan (PG) linked end which utilizes a phosphodiester linkage, has been understudied due to its demanding synthesis. Two convergent routes, both involving a phospho‐donor and an acceptor, are proposed and evaluated. In this work, synthesis of the more efficient route is carried out to obtain the phospho‐donor and PG acceptor. Careful phosphoramidite coupling is utilized to establish the phosphodiester linkage between WTA and PG fragments. These WTA‐PG conjugates will enable more complex studies between the host innate immune response and invading pathogens.