Intramolecular aglycon delivery enables the synthesis of 6-deoxy-β-D-manno-heptosides as fragments of Burkholderia pseudomallei and Burkholderia mallei capsular polysaccharide.
Burkholderia pseudomallei and Burkholderia mallei are potential bioterrorism agents. They express the same capsular polysaccharide (CPS), a homopolymer featuring an unusual [→3)-2-O-acetyl-6-deoxy-β-D-manno-heptopyranosyl-(1→] as the repeating unit. This CPS is known to be one of the main targets of the adaptive immune response in humans and therefore represents a crucial subunit candidate for vaccine development. Herein, the stereoselective synthesis of mono- and disaccharidic fragments of the B. pseudomallei and B. mallei CPS repeating unit is reported. The synthesis of 6-deoxy-β-D-manno-heptosides was investigated using both inter- and intramolecular glycosylation strategies from thio-manno-heptose that was modified with 2-naphthylmethyl (NAP) at C2. We show here that NAP-mediated intramolecular aglycon delivery (IAD) represents a suitable approach for the stereocontrolled synthesis of 6-deoxy-β-D-manno-heptosides without the need for rigid 4,6-O-cyclic protection of the sugar skeleton. The IAD strategy is highly modular, as it can be applied to structurally diverse acceptors with complete control of stereoselectivity. Problematic hydrogenation of the acetylated disaccharides was overcome by using a microfluidic continuous flow reactor.
Université de Poitiers, Institut de Chimie IC2MP, UMR-CNRS 7285, Équipe Synthèse Organique , 4 rue Michel Brunet, 86073 Poitiers, France.
Marielle
M
Tamigney Kenfack
Yves
Y
Blériot
Charles
C
Gauthier
D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000737:chemistry*; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D016667:Bacterial Capsules / Q000737:chemistry*; D042726:Burkholderia mallei / Q000737:chemistry*; D016957:Burkholderia pseudomallei / Q000737:chemistry*; D002240:Carbohydrate Sequence; D003837:Deoxy Sugars / Q000138:chemical synthesis* / Q000737:chemistry; D004187:Disaccharides / Q000737:chemistry*; D006539:Heptoses / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000737:chemistry*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D003837:Deoxy Sugars; D004187:Disaccharides; D006539:Heptoses; D011134:Polysaccharides