Total Synthesis of Complex Nucleoside Antibiotics Ezomycin A1 and A2

Here, we disclose their long-awaited first total synthesis. This convergent and modular strategy is enabled by a stereoselective nickel-catalyzed reductive cross-coupling, a <i>de novo</i> asymmetric carbohydrate synthesis, and a mild (<i>p</i>-Tol)₂SO/Tf₂O-promoted <i>N</i>-glycosylation.

This work not only establishes a unified synthetic route to the ezomycin family but also provides robust methodologies for the precise assembly of sterically demanding, highly functionalized nucleoside natural products.