Synthesis of inner core antigens related to Chlamydia, Pseudomonas and Acinetobacter LPS

Chemical syntheses of inner core determinants have been performed to provid e defined artificial antigens (BSA-glycoconjugates) for characterization of monoclonal antibodies directed against important epitopes residing in the inner core of bacterial lipopolysaccharides. Efficient block synthesis of K do oligosaccharides has been employed to prepare the allyl glycoside [5] co rresponding to the Chlamydia-specific Kdo trisaccharide epitope, to be used in crystallization and NMR (transfer NOe) experiments. Human pathogenic st rains of Pseudomonas aeruginosa of RNA group I contain a highly phosphoryla ted heptose region with a 7-O-carbamoyl L-glycero-D-mannoheptose moiety whi ch may be exploited as immunochemical marker for pathogenic Pseudomonas spe cies. The 7-O-carbamoyl-substituted heptoside [12] as well as the disacchar ides 7-O-carbamoyl-L-gro-alpha-D-manHepp-(1--> 3)-L-gro-alpha-D-manHepp-(1- -> O-Allyl) [23] and alpha-D-GalpNAc-(1-->3)L-gro-alpha-D-manHepp-(1--> 3)- L-gro-alpha-D-manHepp-(1--> O-Allyl) [30] were synthesized via regioselecti ve formation of a 6',7'-O-carbonate group followed by ring opening with NH3 /NH4HCO3 to give the 7-O-carbamate in high yields. Finally, glycosides of t he Kdo-isosteric D-glycero-D-talo-2-octulosonic acid (Ko) occurring in Acin etobacter spp. have been prepared via intermediate orthoester formation and TMSO-triflate-catalyzed rearrangement into alpha-ketosides. Coupling with a Kdo bromide donor and deblocking afforded the disaccharide alpha-Ko-(2--> 4)-alpha-Ko-(2--> O-Allyl) [43].