Highly Optimized β-Mannosylation via p-Methoxybenzyl Assisted Intramolecular Aglycon Delivery

Abstract

Highly efficient and stereoselective β-mannosylation was achieved by using mannosyl thioglycosides 5 and 19. Intramolecular aglycon delivery (IAD) from mixed acetal 12, 15 and 20, obtainable by oxidative coupling of aglycon onto mannosyl thio-glycosides which carry p-methoxybenzyl (PMB) group at C-2 position, was performed by the action of MeOSO2CF3 to afford β-mannosides 13/16/21. It is to be noted that efficiency of IAD was substantially improved by changing the protecting group at the 4- and 6-positions from previously utilized benzylidene to cyclohexylidene (5) or TIPDS (19) group. As a result, it is now possible to perform the β-manno glycosylation in a highly optimized manner to afford di- and trisaccharides with a backbone structure corresponding to asparagine-linked oligosaccharides in 75-85% yield as single stereoisomers.