Glycosylation of an N-Acetylated Glucosamine Disaccharide Using an Orthogonally Protected 3-Iodo-Kdo Fluoride Donor.

Abstract

Kdo (3-Deoxy-d-manno-oct-2-ulosonic acid) is an essential sugar found in bacterial lipopolysaccharides with significant biomedical relevance. This study introduces an orthogonally protected 3-iodo-Kdo fluoride donor and demonstrates its coupling to a pre-synthesized β-(1→6)-linked N-acetylglucosamine disaccharide acceptor as an example. Nuclear magnetic resonance data indicates the presence of an intraresidue hydrogen bond in the distal glucosamine unit. Two complementary glycosylation approaches are explored with an emphasis on achieving high stereoselectivity and minimizing protecting-group manipulation. The orthogonal protection of 3-iodo Kdo fluoride donor offers insights into tailoring Kdo-based donors for specific biomedical applications. While yields vary depending on the approach, they are sufficient to demonstrate the donor's applicability. These findings enable the design of advanced glycomimetic constructs for therapeutic and vaccine research.