A simple access to lactose-derived building blocks required in glycoconjugate synthesis

Lactose was readily transformed into thexyldimethylsilyl (3,4-O-isopropylidene- β-d-galactopyranosyl)-(1 → 4)-β-d-glucopyranoside (5); this compound served as intermediate for the generation of partially O-protected lactose building blocks required in oligosaccharide and glycoconjugate synthesis. Thus, from 5 via per-O-benzoylation, desilylation, trichloroacetimidate formation, glycosylation of the Lemieux spacer, and acid-catalyzed de- O-isopropylidenation methoxycarbonyloctyl (2.6-di-O-benzoyl-β- d-galactopyranosyl)-(1 → 4)-2.3.6-tri-O-benzoyl-β-d- glucopyranoside (12) was obtained. Regioselective benzoylation of 5 with benzoyl cyanide under various conditions afforded 3-O- (13), 2,3,2′- O- (14), 3,2′-O- (16), and 2,2′-O-unprotected (17) lactoside, respectively. De-O-isopropylidenation of 16 gave thexyldimethylsilyl (6-O-benzoyl-β-d-galactopyranosyl)- (1 → 4)-2,6-di-O-benzoyl-β-d-glucopyranoside (18), an important 2′,3′,4′-O-unprotected lactose derivative. Fucosylation of 13 and then de-O-isopropylidenation afforded thexyldimethylsilyl (2,6-di-O-benzoyl-β-d-galactopyranosyl)-(1 → 4)-[(3,4-di- O-acetyl-2-O-benzoyl-α-l-fucopyranosyl)-(1 → 3)]-2,6-di-O- benzoyl-β-d-glucopyranoside(21), an important fucosyllactose building block.