Enantioselective Total Synthesis of the Neurotoxin Caramboxin.

Herein, we report the first and efficient asymmetric total synthesis of the neurotoxin (-)-caramboxin. The key to success is the creation of a stereogenic center by using enantioselective catalytic phase-transfer α-alkylation of glycine imines, affording this unusual α-amino acid in good yields and up to 99% ee. This work validates the configuration of the natural product.

Metal-free synthesis of γ-ketosulfones through Brønsted acid-promoted conjugate addition of sulfinamides.

A straightforward and general metal-free method has been developed to add sufinamide-derived sulfone units on Michael acceptors under mild conditions. This reaction enables the preparation of a large variety of original γ-ketosulfones, of which only a few synthetic methods have been reported. The mild reaction conditions used tolerate a wide diversity of functional groups and empower the implementation of a late-stage functionalisation strategy.

Carbon Nucleophile-Initiated Rauhut-Currier Reaction: An Atom-Economical Synthesis of Highly Functionalized Carbocycles.

A Rauhut-Currier reaction cascade is achieved in the presence of carbon nucleophiles under mild conditions. This original atom-economical transformation enables an efficient one-pot synthesis of densely substituted carbocycles from readily accessible substrates. The key promoter role of the cesium cation in the cascade process was demonstrated.

Identification of a pre-active conformation of a pentameric channel receptor.

Pentameric ligand-gated ion channels (pLGICs) mediate fast chemical signaling through global allosteric transitions. Despite the existence of several high-resolution structures of pLGICs, their dynamical properties remain elusive. Using the proton-gated channel GLIC, we engineered multiple fluorescent reporters, each incorporating a bimane and a tryptophan/tyrosine, whose close distance causes fluorescence quenching.

Barbiturates Bind in the GLIC Ion Channel Pore and Cause Inhibition by Stabilizing a Closed State.

Barbiturates induce anesthesia by modulating the activity of anionic and cationic pentameric ligand-gated ion channels (pLGICs). Despite more than a century of use in clinical practice, the prototypic binding site for this class of drugs within pLGICs is yet to be described. In this study, we present the first X-ray structures of barbiturates bound to GLIC, a cationic prokaryotic pLGIC with excellent structural homology to other relevant channels sensitive to general anesthetics and, as shown here, to barbiturates, at clinically relevant concentrations.