Nonreducing Sugar Scaffold Enables the Development of Immunomodulatory TLR4-specific LPS Mimetics with Picomolar Potency.

Innate immune defense mechanisms against infection and cancer encompass the modulation of pattern recognition receptor (PRR)-mediated inflammation, including upregulation of various transcription factors and the activation of pro-inflammatory pathways important for immune surveillance. Dysfunction of PRRs-mediated signaling has been implicated in cancer and autoimmune diseases, while the overactivation of PRRs-driven responses during infection can lead to devastating consequences such as acute lung injury or sepsis. We used crystal structure-based design to develop immunomodulatory lipopolysaccharide (LPS) mimetics targeting one of the ubiquitous PRRs, Toll-like Receptor 4 (TLR4).

Versatile approach towards fully desymmetrized trehalose with a novel set of orthogonal protecting groups.

Trehalose-containing glycans play an essential role in bacterial pathogenesis, host-pathogen interaction, and cell signaling. The investigation of trehalose uptake and metabolism in using synthetic desymmetrized trehalose probes is an important approach for the development of diagnostic tools and potential therapeutics for tuberculosis. Trehalose-derived mycobacterial glycolipids activate the innate immune response through recognition by the C-type lectin Mincle, justifying efforts to develop novel trehalose-based Mincle-dependent adjuvants.

Regioselective 3-O-Substitution of Unprotected Thiodigalactosides: Direct Route to Galectin Inhibitors.

The synthesis of tailored bioactive carbohydrates usually comprises challenging (de)protection steps, which lowers synthetic yields and increases time demands. We present here a regioselective single-step introduction of benzylic substituents at 3-hydroxy groups of β-d-galactopyranosyl-(1→1)-thio-β-d-galactopyranoside (TDG) employing dibutyltin oxide in good yields. These glycomimetics act as inhibitors of galectins-human lectins, which are biomedically attractive targets for therapeutic inhibition in, for example, cancerogenesis.

Enantioselective Synthesis of All-Carbon Quaternary Centers Structurally Related to Amaryllidaceae Alkaloids.

Enantioselective synthesis of all-carbon quaternary centers remains a considerable challenge for synthetic organic chemists. Here, we report a two-step protocol to synthesize such centers including tandem cyclization/Suzuki cross-coupling followed by halocarbocyclization. During this process, two rings, three new C-C bonds and a stereochemically defined all-carbon quaternary center are formed.