Chemical Synthesis of the Nonreducing Hexasaccharide Fragment of Axinelloside A Based on a Stepwise Glycosylation Approach.

An expedient synthesis of the nonreducing hexasaccharide fragment of axinelloside A has been completed via a linear stepwise glycosylation approach. Challenges involved in the synthesis include the highly stereoselective construction of five consecutive 1,2-<i>cis</i>-glycosidic linkages and the formation of a sterically crowded 2,3-disubstituted l-fucoside subunit. Protecting group-directing glycosylation strategies such as the remote participation effect of the benzoyl substituent and the stereocontrolling effect of the 4,6-<i>O</i>-benzylidene group were employed for the synthesis of the desired 1,2-<i>cis</i>-glycosidic linkages. Moreover, the 2,3-branched l-fucoside framework was established through a 3-<i>O</i> and then 2-<i>O</i> glycosylation sequence in which the 3-hydroxyl group of the core l-fucose unit was glycosylated first and then the 2-hydroxyl. The synthetic hexasaccharide is properly protected, so it can be employed as a precursor to synthesize its natural form.