Complex oligosaccharide investigations: synthesis of an octasaccharide incorporating the dimeric Le(x) structure of PSGL-1.

Abstract

The synthesis of an octasaccharide containing the dimeric Le(x) oligosaccharide structure found in PSGL-1 carbohydrate chains is reported. Several approaches were investigated employing regioselective and stereoselective glycosylation procedures, and a novel Lewis(x) trisaccharide donor, 7, was prepared and utilized as a key intermediate building block in the scheme developed for the construction of octasaccharide 3. Toward the preparation of 7, investigations into the influence of different protecting groups upon the relative reactivities of disaccharide acceptor moieties, 25 or 26, and the fucosyl donors, 10 and 11, were conducted using similar glycosylating conditions. Dramatic differences were noted between the effects of electron-donating and electron-withdrawing groups upon the reactivity of the acceptor hydroxyl. A similar effect upon the glycosylating capability of the donor molecule was, likewise, observed. The repeat use of donor 7 was instrumental in the synthesis of the desired dimeric octasaccharide structure 3. The structure and purity of 3 and important intermediates were fully characterized by DQF-COSY, TOCSY, ROESY, and ESI mass spectroscopy.