Synthesis of zwitterionic 1,1'-glycosylphosphodiester: a partial structure of galactosamine-modified Francisella lipid A.

Synthesis of a "double glycosidic" phosphodiester comprising anomeric centers of two 2-amino-2-deoxy-sugars is reported. The carbohydrate epitope of Francisella lipid A modified with α-d-galactosamine at the anomerically linked phosphate has been stereoselectively prepared and coupled to maleimide-activated bovine serum albumin via an amide-linked thiol-terminated spacer group. H-Phosphonate and phosphoramidite approaches have been explored for the coupling of 4,6-DTBS-2-azido-protected GalN lactol and peracetylated spacer-equipped reducing βGlcN(1→6)GlcN disaccharide via phosphodiester linkage. Deprotection conditions preserving the integrity of the labile glycosidic zwitterionic phosphodiester were elaborated.