title: Total synthesis of legionaminic acid as basis for serological studies.
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 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.
authors: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces , Am Mühlenberg 1, 14476 Potsdam, Germany.
authors: Stefan
authors: S
authors: Matthies
authors: Pierre
authors: P
authors: Stallforth
authors: Peter H
authors: PH
authors: Seeberger
mesh_terms: D060326:Chemistry Techniques, Synthetic; D006027:Glycosides / Q000276:immunology; D006801:Humans; D046228:Microarray Analysis; D012698:Serologic Tests / Q000379:methods*; D012794:Sialic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013912:Threonine / Q000737:chemistry
chemical_list: C110570:5,7-diacetamido-8-O-acetyl-3,5,7,9-tetradeoxy-glycero-talo-nonulosonic acid; D006027:Glycosides; D012794:Sialic Acids; D013912:Threonine