Total Synthesis of Legionaminic Acid as Basis for Serological Studies

Legionaminic
acid is a nine-carbon diamino monosaccharide that
is found coating the surface of various bacterial human pathogens.
Its unique structure makes it a valuable biological probe, but access
via isolation is difficult and no practical synthesis has been reported.
We describe a stereoselective synthesis that yields a legionaminic
acid building block as well as linker-equipped conjugation-ready legionaminic
acid starting from cheap d-threonine. To set the desired
amino and hydroxyl group pattern of the target, we designed a concise
sequence of stereoselective reactions. The key transformations rely
on chelation-controlled organometallic additions and a Petasis multicomponent
reaction. The legionaminic acid was synthesized in a form that enables
attachment to surfaces. Glycan microarray containing legionaminic
acid revealed that human antibodies bind the synthetic glycoside.
The synthetic bacterial monosaccharide is a valuable probe to detect
an immune response to bacterial pathogens such as Legionella
pneumophila, the causative agent of Legionnaire’s
disease.