Use of Olefin Cross-Metathesis to Release Azide-Containing Sugars from Solid Support

The octenediol linker used during automated oligosaccharide assembly is cleaved by olefin cross-metathesis. Until now, this linker could not be applied to sugars containing azides. A detailed study of the cleavage reaction served as basis for the development of a new protocol using the [(H2Imes)(3-Br-py)2(Cl)2RuCHPh] catalyst and 1-pentene. Efficient release of azide-protected carbohydrates from solid support can be readily achieved

Total Synthesis of the Bacteroides fragilis Zwitterionic Polysaccharide A1 Repeating Unit

Nearly all bacteria capsular polysaccharides are T-cell-independent antigens that do not promote immunoglobulin class switching from IgM to IgG nor memory responses. In contrast, zwitterionic polysaccharides activate T-cell-dependent immune responses by major histocompatability complex class II presentation, a mechanism previously believed to be reserved for peptidic antigens. The best studied zwitterionic polysaccharide, polysaccharide A1 (PS A1) is found on the capsule of the commensal bacteria Bacteroides fragilis. Its potent immunomodulatory properties have been linked to postoperative intra-abdominal abscess formation. Here, we report the synthesis of the PS A1 tetrasaccharide repeating unit (2) as a tool to investigate the biological role of this polysaccharide. A modular synthetic strategy originating from the reducing end of the PS A1 repeating unit was unsuccessful and illustrated the limitations of glycosylation reactions between highly armed glycosylating agents and poor nucleophiles. Thus, a [3 + 1] glycosylation relying on trisaccharide 5 and pyruvalated galactose 6 was used to complete the first total synthesis of the PS A1 repeating unit (2)

Highly Efficient Continuous Flow Reactions Using Singlet Oxygen as a “Green” Reagent

Described is a new method for the efficient in situ production of singlet oxygen in a simple continuous flow photochemical reactor. The extremely large interfacial area generated by running the biphasic mixture in a narrow channel at a high flow rate ensures high throughput as well as fast and efficient oxidation of various alkenes, 1,3-dienes, and thioethers on a preparative scale

Total Synthesis of the Bacteroides fragilis Zwitterionic Polysaccharide A1 Repeating Unit

Nearly all bacteria capsular polysaccharides are T-cell-independent antigens that do not promote immunoglobulin class switching from IgM to IgG nor memory responses. In contrast, zwitterionic polysaccharides activate T-cell-dependent immune responses by major histocompatability complex class II presentation, a mechanism previously believed to be reserved for peptidic antigens. The best studied zwitterionic polysaccharide, polysaccharide A1 (PS A1) is found on the capsule of the commensal bacteria Bacteroides fragilis. Its potent immunomodulatory properties have been linked to postoperative intra-abdominal abscess formation. Here, we report the synthesis of the PS A1 tetrasaccharide repeating unit (2) as a tool to investigate the biological role of this polysaccharide. A modular synthetic strategy originating from the reducing end of the PS A1 repeating unit was unsuccessful and illustrated the limitations of glycosylation reactions between highly armed glycosylating agents and poor nucleophiles. Thus, a [3 + 1] glycosylation relying on trisaccharide 5 and pyruvalated galactose 6 was used to complete the first total synthesis of the PS A1 repeating unit (2)

<i>De Novo</i> Synthesis of the Bacterial 2-Amino-2,6-Dideoxy Sugar Building Blocks d‑Fucosamine, d‑Bacillosamine, and d‑Xylo-6-deoxy-4-ketohexosamine

The cell-surface glycans on bacteria contain many monosaccharides that cannot be obtained by isolation from natural sources. Availability of differentially protected monosaccharides is therefore often limiting access to potential oligosaccharide vaccine antigens. d-Fucosamine, d-bacillosamine, and d-xylo-2,6-deoxy-4-ketohexosamine building blocks were prepared via a divergent <i>de novo</i> synthesis from l-Garner aldehyde. The route relies on a chelation-control assisted organometallic addition and an <i>anti</i>-selective dihydroxylation reaction

Anomeric Phosphorodithioates as Novel Glycosylating Agents

Anomeric Phosphorodithioates as Novel Glycosylating Agent

Cap-and-Tag Solid Phase Oligosaccharide Synthesis

A new “cap-and-tag” strategy is applied to solid phase oligosaccharide synthesis. Acetyl-capping and fluorous-tagging allowed for the facile separation of the desired F-tagged oligosaccharide from the acetyl-capped deletion sequences using fluorous solid phase extraction. To illustrate this approach, a protected Glc-β-(1→6)-Man-α-(1→6)-Glc-β-1→pentenyl trisaccharide was synthesized

Anomeric Phosphorodithioates as Novel Glycosylating Agents

Anomeric Phosphorodithioates as Novel Glycosylating Agent

Solution and Solid-Support Synthesis of a Potential Leishmaniasis Carbohydrate Vaccine

The synthesis of a potential carbohydrate vaccine for the parasitic disease leishmaniasis is described. New solution- and solid-phase synthetic strategies were explored for the assembly of a unique tetrasaccharide antigen found on the Leishmania lipophosphoglycan. An initial solution-phase synthesis relied on thioglycosides as building blocks and the establishment of the central disaccharide from lactal via an oxidation−reduction sequence. A second approach was completed both in solution and on solid support. The solid-phase synthesis relied on assembly from monosaccharide units and was used to evaluate different glycosylating agents in the efficient installation of the galactose β-(1→4) mannoside. Glycosyl phosphates proved most successful in this endeavor. This first solid-phase synthesis of the Leishmania cap provided rapid access to the tetrasaccharide in 18% overall yield while requiring only a single purification step. The synthetic cap tetrasaccharide was conjugated to the immunostimulator Pam3Cys to create fully synthetic carbohydrate vaccine 1 and to the carrier protein KLH to form semisynthetic vaccine 2. Currently, both constructs have entered initial immunological experiments in mice targeted at the development of a vaccine against the parasitic disease leishmaniasis

<i>De Novo</i> Synthesis of the Bacterial 2-Amino-2,6-Dideoxy Sugar Building Blocks d‑Fucosamine, d‑Bacillosamine, and d‑Xylo-6-deoxy-4-ketohexosamine

The cell-surface glycans on bacteria contain many monosaccharides that cannot be obtained by isolation from natural sources. Availability of differentially protected monosaccharides is therefore often limiting access to potential oligosaccharide vaccine antigens. d-Fucosamine, d-bacillosamine, and d-xylo-2,6-deoxy-4-ketohexosamine building blocks were prepared via a divergent <i>de novo</i> synthesis from l-Garner aldehyde. The route relies on a chelation-control assisted organometallic addition and an <i>anti</i>-selective dihydroxylation reaction