From solution phase to "on-column" chemistry: Trichloroacetimidate-based glycosylation promoted by perchloric acid-silica

Activation of ester-protected glycosyl trichloroacetimidate donors by perchloric acid immobilized on silica afforded 1,2-trans disaccharides in 60-90% yields. Applying this approach to one-pot sequential glycosylation resulted in efficient syntheses of the N-linked glycan trimannoside and LeX and LeA trisaccharides in very good yield (76%, 62%, and 59% yields, respectively). Solution phase reactions were also translated to a solid phase format; priming the top of a standard silica chromatography column with perchloric acid immobilized on silica facilitated "on-column" glycosylation with subsequent "in situ" purification of products. Coupling yields from this approach were comparable to those obtained from the corresponding solution-phase disaccharide couplings. A series of glycosylated amino acids were also synthesized in high yield with use of the on-column approach. © 2005 American Chemical Society.