| Kingella kingae is a aerobic facultative anaerobic gram-negative bacterium that has emerged as a common etiology of series of diseases in children aged 6-36 months.The most common types are septic arthritis,osteomyelitis and bacteremia.Recent evidence indicated that Kingella kingae produces a polysaccharide capsule,analysis of the extracts revealed one basis of the bacterial surface is?3)-?-GaIpNAc-(1?5)-?-Kdop-(2? structure,which is made up of N-acetylgalactosamine(GalNAc)and 3-deoxy-D-manno-oct-2-ulsonic acid(Kdo).It is of great significance to synthesize the repeated uinits,and to study these molecules'immunocompetence in the development of antibacterial vaccine.Since the construction of Kdo blocks in this repeating unit is troublesome and the glycosylation activity,especially 5-OH,is even lower,it is very challenging to construct this repeating unit.Herein,we adopt the Cornforth reaction for the synthesis of Kdo monosaccharide intermediate,and condensed it with ortho-alkynylbenzoate to form the homologous Kdo donors.Under the catalysis of gold Couple,the Kdo donors successfully coupled with Linker and get ?-Kdo stereoselectively.Then we tried and optimized the glycosylation reactions of ?-Kdo and galactosamine thioside,trifluoroacetyl imide and ortho-alkynylbenzoate donors we prepared,achieved the first connection of ?-(1 ? 5)linked Kdo and amino sugar.Ortho-protected ?-GalNAc-(1?5)-?-Kdo disaccharides are deprotected to form antigens with amyl amine-linker at the ends,which can be further linked to the carrier protein and arrays for relevant immunoactivity tests to evaluate its potential as a saccharide synthetic vaccine. |
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