Differential O-3/O-4 regioselectivity in the glycosylation of α and β anomers of 6-O-substituted N-dimethylmaleoyl-protected d-glucosamine acceptors

Abstract

An assessment of the relative O-3/O-4 reactivities of both methyl α- and β- d-glycosides of N-dimethylmaleoyl (DMM) d-glucosamine acceptors protected at O-6 with benzoyl (Bz), benzyl (Bn), and tert-butyldiphenylsilyl (TBDPS) groups is presented using per-O-benzoylated β- d-galactofuranosyl and per-O-acetylated α- d-galactopyranosyl trichloroacetimidates as glycosyl donors. Using the former donor, the α anomer of the 6-O-benzoylated compound gave exclusive substitution at O-3, whereas the other two compounds with α-configuration kept this site as preferential. The β anomer of the 6-O-benzoylated compound gave the same amounts of reaction products on O-3 and O-4, whereas the other β analogs carried a more reactive O-4. The same reactions were carried out using as donor the less-reactive per-O-acetylated α- d-galactopyranosyl trichloroacetimidate. Although the same trend was found to occur, the O-4 was always relatively more reactive with the pyranosyl donor than with the furanosyl donor, when keeping the remaining factors constant. Furthermore, the β anomers of the acceptor gave almost exclusive substitution at O-4. These observations confirm and extend the utility of these ‘matching’ donor and acceptor reactivities.