ADP-heptose is a newly identified pathogen-associated molecular pattern of .

During an infection, the detection of pathogens is mediated through the interactions between pathogen-associated molecular patterns (PAMPs) and pathogen recognition receptors. β-Heptose 1,7-bisphosphate (βHBP), an intermediate of the lipopolysaccharide (LPS) biosynthesis pathway, was recently identified as a bacterial PAMP. It was reported that βHBP sensing leads to oligomerization of TIFA proteins, a mechanism controlling NF-κB activation and pro-inflammatory gene expression.

Synthetic Studies toward the C14-C29 Fragment of Mirabalin.

A convergent synthesis of one isomer of the C14-C29 fragment of mirabalin is disclosed. The key steps include a Marshall allenylation, a Mukaiyama aldol reaction and a Crimmins aldolization, which allow the control of 10 out of 25 stereogenic centers present in the molecule.

Iron- and indium-catalyzed reactions toward nitrogen- and oxygen-containing saturated heterocycles.

A myriad of natural and/or biologically active products include nitrogen- and oxygen-containing saturated heterocycles, which are thus considered as attractive scaffolds in the drug discovery process. As a consequence, a wide range of reactions has been developed for the construction of these frameworks, much effort being specially devoted to the formation of substituted tetrahydropyrans and piperidines. Among the existing methods to form these heterocycles, the metal-catalyzed heterocyclization of amino- or hydroxy-allylic alcohol derivatives has emerged as a powerful and stereoselective strategy that is particularly interesting in terms of both atom-economy and ecocompatibility.

Heck coupling using a vinyliodo-MIDA boronate: an efficient and modular access to polyene frameworks.

A simple Heck coupling between an alkenyl iodo-boronate and a variety of terminal olefins is disclosed. This method gives access to a wide range of dienic moieties including valuable bis-functionalized dienes. The synthetic potential of the coupling reaction is demonstrated by a short and modular preparation of several tetraenic compounds.

Synthetic strategy toward the C44-C65 fragment of mirabalin.

A convergent and flexible stereoselective synthesis of one isomer of the C44-C65 fragment of mirabalin is described. The key steps include organocatalytic aldolization, ruthenium-catalyzed asymmetric hydrogenation, amide formation, Marshall stereoselective allenylation, and the Nozaki-Hiyama-Kishi reaction.

FeCl3·6H2O, a catalyst for the diastereoselective synthesis of cis-isoxazolidines from N-protected δ-hydroxylamino allylic acetates.

An ecofriendly and diastereoselective synthesis of cis-3,5-disubstituted isoxazolidines through the FeCl3·6H2O-catalyzed cyclization of δ-hydroxylamino allylic acetates is described. The synthetic potential of these products is highlighted by the preparation of several functionalized 1,3-amino alcohol precursors.

Optimization of a Novel Series of TRPV4 Antagonists with In Vivo Activity in a Model of Pulmonary Edema.

High-throughput screening and subsequent hit optimization identified 1-piperidinylbenzimidazoles, exemplified by compound 1, as TRPV4 inhibitors. Lead optimization identified potent TRPV4 blocker 19, which has good target activity and pharmacokinetic properties. Inhibitor 19 was then profiled in an in vivo rat model, demonstrating its ability to inhibit TRPV4-mediated pulmonary edema.