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

Org Lett. 2022 Oct 7;24(39):7088-7094. doi: 10.1021/acs.orglett.2c02618. Epub 2022 Sep 28.

Abstract

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-cis-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-O-benzylidene group were employed for the synthesis of the desired 1,2-cis-glycosidic linkages. Moreover, the 2,3-branched l-fucoside framework was established through a 3-O and then 2-O 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fucose*
  • Glycosides*
  • Glycosylation
  • Lipopolysaccharides
  • Oligosaccharides

Substances

  • Glycosides
  • Lipopolysaccharides
  • Oligosaccharides
  • axinelloside A
  • Fucose