Synthesis of stable C-phosphonate analogues of Neisseria meningitidis group A capsular polysaccharide structures using modified Mitsunobu reaction conditions.
Examples of synthetic C-phosphonate analogues of microbial polysaccharide structures containing inter-residue phosphodiester linkages are most rare. The successful construction of such analogues of the Neisseria meningitidis Group A capsular polysaccharide is described. Using a modified Mitsunobu reaction (tris(4-chlorophenyl)phosphine, DIAD, excess of Et3N) between an anomeric C-phosphonate monoester and a 6-OH ManNAc acceptor a high yield (88%) of a dimer was obtained. Transformation of the dimer into a new 6-OH acceptor through deacetylation and further reaction with the elongating C-phosphonate monomer employing the same conditions afforded the trimer in 92% yield. Iteration of the procedure then afforded the tetramer with a coupling yield of 85%. The di-, tri- and tetramer were deprotected to give target structures ready for conjugation to a carrier protein and subsequent immunological evaluation.
Teodorović
Peter
P
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, S-106 91, Stockholm, Sweden.
Slättegård
Rikard
R
Oscarson
Stefan
S
D002236:Carbohydrate Conformation; D038381:Neisseria meningitidis, Serogroup A / Q000378:metabolism*; D063065:Organophosphonates / Q000737:chemistry*; D011135:Polysaccharides, Bacterial / Q000737:chemistry* / Q000378:metabolism*
D063065:Organophosphonates; D011135:Polysaccharides, Bacterial