Total Synthesis of Legionaminic Acid as Basis for Serological Studies

Matthies S, Stallforth P, Seeberger PH (2015) Total Synthesis of Legionaminic Acid as Basis for Serological Studies J Am Chem Soc 137, 2848-2851.

Abstract

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 Dthreonine.
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.

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