Synthesis of carboxyl-reduced analogues related to the Chlamydia-specific Kdo trisaccharide epitope.

The disaccharides allyl O-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)-(2-->4)-3-deoxy-a lph a-D- manno-2-octulopyranoside (8), allyl O-(3-deoxy-alpha-D-manno-2-octulopyranosyl)-(2-->8)-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosidonate) (24), and allyl O-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)-(2-->8)-3-deoxy-a lph a-D- manno-2-octulopyranoside (35), and the trisaccharides allyl O-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)-(2-->8)-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)-(2-->4)-3-deoxy-a lph a-D-manno-2-octulopyranoside (13) and allyl O-(3-deoxy-alpha-D-manno-2-octulopyranosyl)-(2-->8)-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)-(2-->4)-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosidonate) (30) were prepared. The ketosidic linkages were formed in good yields and high stereoselectivity by BF3 . Et2O-catalyzed reaction of the per-O-acetylated 3-deoxy-alpha-D-manno-2-octulopyranosyl fluoride derivative (16) with 8-O-SiButMe2 derivatives 19 and 21. Coupling reactions using the Kdo monosaccharide bromide derivative 4 or the alpha-(2-->8)-linked Kdo disaccharide bromide derivatives 9 and 26 were performed under Helferich conditions in MeCN or MeNO2, respectively. The disaccharide halides were prepared in good overall yields starting from the readily available allyl beta-glycoside of Kdo. The deprotected oligosaccharides correspond to the genus-specific lipopolysaccharide epitope of Chlamydia and part structures thereof, containing the carboxyl-reduced Kdo-residues at the distal and proximal position of the Kdo trisaccharide epitope, respectively.