Prearranged glycosides, 2. Intramolecular glycosylation of prearranged saccharides as a novel strategy for the construction of β‐L‐rhamnosidic linkages

Abstract

AbstractDisaccharides containing a β‐L‐rhamnosyl residue were prepared by a novel intramolecular glycosylation strategy. Thus, suitably benzyl‐protected L‐rhamnosyl donors (ethyl and phenyl 1‐thiorhamnoside 7, 18) were prearranged in positions 2 and 3 with benzyl 2‐O‐benzoyl‐4,6‐O‐benzylidene‐α‐D‐glucopyranoside 8 in position 3 by a malonyl, succinyl and phthaloyl bridge, respectively, to give the corresponding connected saccharides 9, 12, 16 and 20. After regioselective opening of the benzylidene ring of the glucoside residue to give compounds 10, 13, 17 and 21, the latter afforded the 3,2′‐ and 3,3′‐bridged disaccharides 22–25 upon intramolecular glycosylation with a thiophilic reagent. The anomeric selectivity of this intramolecular glycosylation is strongly influenced by the nature of the alkanoyl and aroyl bridge, its position at the rhamnosyl residue and the solvent used for the coupling. Best results were obtained in acetonitrile with the succinyl „spacer”︁ attached to position 2 of the phenyl 1‐thiorhamnoside and position 3 of the glucoside that afforded the corresponding β‐(1→4)‐linked disaccharide 22β in 76% yield.