Expedient Synthesis of the Cap Tetrasaccharide of <i>Leishmania</i> Lipophosphoglycan

Leishmaniasis remains an ignored tropical disease with urgent need for safe and effective vaccines. The lipophosphoglycans (LPGs) of Leishmania parasites is a key virulence factor, and its terminal cap tetrasaccharide represents a structurally conserved antigen suitable for vaccine development. Herein, we report a concise and practical route to synthesize the cap tetrasaccharide. This synthesis strategy highlights (i) regioselective axial benzoylation of mannosyl units via the “cyanide effect,” providing quick and orthogonally protected building blocks in large scale, and (ii) highly stereoselective glycosidation under AuCl 3 – t BuCN cooperative catalysis, which ensures efficient formation of challenging β ‐(1,4)‐galactosidic linkages without neighboring participation. These protocols are operationally simple, minimize protecting group manipulations, and are highly reproducible, thus enabling in‐depth biological studies and translational implementation.