n-pentenyl glycosides in the efficient assembly of the blood group substance B tetrasaccharide

The fact that n-pentenyl glycosides (nPGs) are stable to a wide variety of reaction conditions but yet can be chemospecifically activated is advantageous for the efficient, convergent assembly of oligosaccharides. The nPGs are prepared directly from the aldose or by normal glycoside-forming reactions, and by using N-iodosuccinimide/triethylsilyl triflate as the iodonium source, even "disarmed" glycosyl donors react within minutes. The four monosaccharide components of the human blood-group determinant B are prepared with full or partial protection as required. Assembly of the tetrasaccharide then requires only five steps, three to give, in sequence, the disaccharide (68%), trisaccharide (82%), and tetrasaccharide (91%), the other two steps being required to deprotect hydroxyl groups at the di- and tri-saccharide levels for the ensuing coupling reactions. Advances in synthetic oligosaccharide chemistry are key to understanding the biological functions of complex carbohydrates 1 such as cell-surface glycoproteins, glycolipids, and the antigenic determinants of blood-group substances 2. Within the past 15 years, the latter have attracted considerable attention, synthetic activity having been pioneered by Lemieux and coworkers 3, and pursued by Paulsen 4 and others 5,6. Their endeavors, which employed some novel carbohydrate transformations, have culminated in the syntheses of blood-group antigenic determinants such as the lacto-N-biose, 1, and the blood group substances A and B (2 and 3). [GRAPHICS] We recently showed that n-pentenyl glycosides (nPGs) serve the contrasting functions of excellent protection for, as well as chemospecific liberation of, the anomeric center.7 Thus the activating group can be attached at the anomeric center of the aldose directly (as in the preparation of 17a, Scheme 4) or at an early stage, (as in the preparation of 8, Scheme 2), since it can survive a wide variety of transformations, and yet be activated chemospecifically when required.8 The use of protecting groups to electronically arm or disarm glycosides, was first demonstrated with nPGs,8a,8c and more recently the use of cyclic acetals as agents for obtaining torsionally disarmed substrates was disclosed.9 However disarmed substrates can be readily activated by use of appropriate promoters,10 hence coupling strategies of nPGs can be reagent-controlled or substrate-controlled.11