Chalcones and Five-Membered Heterocyclic Isosteres Bind to Alpha Synuclein Fibrils in Vitro

Construction of Five-Membered Heterocyclic Compounds via Radical Cyclization

Facile formation of five-membered N-heterocyclic zirconacycloallenoids.

The reaction of η(2)-iminozirconocene chloride complexes with trimethylsilylethynyl lithium leads to rapid C-C coupling at room temperature to yield the corresponding five-membered aza-zirconacycloallenoids. Such compounds were also obtained by trapping of in situ generated zirconocene with alkynyl imines.

Palladium-Catalyzed Amination of Unprotected Five-Membered Heterocyclic Bromides

An efficient method for the palladium-catalyzed amination of unprotected bromoimidazoles and bromopyrazoles is presented. The transformation is facilitated by the use of our newly developed Pd precatalyst based on the bulky biarylphosphine ligand tBuBrettPhos (L4). The mild reaction conditions employed allow for the preparation of a broad scope of aminoimidazoles and aminopyrazoles in moderate ...

Aggregated and monomeric alpha-synuclein bind to the S6' proteasomal protein and inhibit proteasomal function.

The accumulation of aggregated alpha-synuclein is thought to contribute to the pathophysiology of Parkinson's disease, but the mechanism of toxicity is poorly understood. Recent studies suggest that aggregated proteins cause toxicity by inhibiting the ubiquitin-dependent proteasomal system. In the present study, we explore how alpha-synuclein interacts with the proteasome. The proteasome exists...

Scope and mechanism of palladium-catalyzed amination of five-membered heterocyclic halides.

Detailed studies have been conducted to determine the activity of palladium catalysts for the amination of five-membered heterocyclic halides and to determine the factors that control the scope of this reaction. Palladium-catalyzed aminations of the electron-rich furanyl, thiophenyl, and indolyl halides and of the related 2-halogenated thiazoles, benzimidazole, and benzoxazole have been shown t...