Silver-Catalyzed C(sp³)–H Chlorination

A silver-catalyzed chlorination of benzylic, tertiary, and secondary C­(sp³)–H bonds was developed. The reaction proceeded with as low as 0.2 mol % catalyst loading at room temperature under air atmosphere with synthetically useful functional group compatibility. The regioselectivity and reactivity tendencies suggest that the chlorination proceeded through a radical pathway, but an intermediate alkylsilver species cannot be ruled out

Visualized and Quantitative Conformational Analysis of Peptidomimetics

Protein–protein interactions (PPIs) are fundamentally important and challenging drug targets. Peptidomimetic molecules of various types have been developed to modulate PPIs. A particularly promising drug discovery strategy, structural peptidomimetics, was designed based on special mimicking of side-chain Cα–Cβ bonds. It is simple and versatile. Nevertheless, no quantitative method has been established to evaluate its similarity to a target peptide motif. We developed two methods that enable visual, comprehensive, and quantitative analysis of peptidomimetics: peptide conformation distribution (PCD) plot and peptidomimetic analysis (PMA) map. These methods specifically examine multiple side-chain Cα–Cβ bonds of a peptide fragment motif and their corresponding bonds (pseudo-Cα–Cβ bonds) in a mimetic molecule instead of φ and ψ angles of a single amino acid in the traditional Ramachandran plot. The PCD plot is an alignment-free method, whereas the PMA map is an alignment-based method providing distinctive and complementary analysis. Results obtained from analysis using these two methods indicate our multifacial α-helix mimetic scaffold 12 as an excellent peptidomimetic that can precisely mimic the spatial positioning of side-chain functional groups of α-helix. These methods are useful for visualized and quantified evaluation of peptidomimetics and for the rational design of new mimetic scaffolds