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

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 2,3branched 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.

Synthesis of the Reducing‐end Hexasaccharide Fragment of Marine Lipopolysaccharide Axinelloside A

“…[5] Recently, Yang and co-workers revealed a synthesis of the nonreducing-end hexasaccharide fragment (units GÀ L) via stepwise sugar assembly. [6] However, synthetic route toward the reducing-end oligosaccharide fragment (units AÀ F) and the dodecasaccharide backbone remains unknown.…”

“…The Walczak group reported the preparation of the terminal monosaccharide fragments, i. e., the scyllo ‐inositol (unit A) [4] and the sulfated D‐galactopyranosyl liposaccharide (unit K) [5] . Recently, Yang and co‐workers revealed a synthesis of the nonreducing‐end hexasaccharide fragment (units G−L) via stepwise sugar assembly [6] . However, synthetic route toward the reducing‐end oligosaccharide fragment (units A−F) and the dodecasaccharide backbone remains unknown.…”

Convergent Synthesis of the Nonreducing Hexasaccharide Fragment and the Dodecasaccharide Scaffold of Marine Lipopolysaccharide Axinelloside A

“…Shortly thereafter, the same group synthesized three sulfated D‐galactosyl liposaccharides reminiscent of the nonreducing end of 1 [3] . In 2022, Yang and co‐workers described a chemical synthesis of the protected nonreducing hexasaccharide fragment through a stepwise [3+1+1+1] assembly [4] . Very recently, we disclosed the synthesis of the linear reducing end hexasaccharide fragment; [5] herein, we describe the convergent syntheses of the branched nonreducing hexasaccharide fragment as well as a properly protected dodecasaccharide backbone of axinelloside A ( 1 ).…”