Macrocyclic Oxindole Peptide Epoxyketones-A Comparative Study of Macrocyclic Inhibitors of the 20S Proteasome.

Peptide macrocycles have recently gained attention as protease inhibitors due to their metabolic stability and specificity. However, the development of peptide macrocycles with improved binding potency has so far been challenging. Here we present macrocyclic peptides derived from the clinically applied proteasome inhibitor carfilzomib with an oxindole group that mimics the natural product TMC-95A.

Electrophotocatalytic C-H Functionalization of Ethers with High Regioselectivity.

The highly regioselective electrophotocatalytic C-H functionalization of ethers is described. These reactions are catalyzed by a trisaminocyclopropenium (TAC) ion at mild electrochemical potential with visible light irradiation. Ethers undergo oxidant-free coupling with isoquinolines, alkenes, alkynes, pyrazoles, and purines with typically high regioselectivity for the less-hindered α-position.

Selective Conversion of Carbon Dioxide to Formaldehyde via a Bis(silyl)acetal: Incorporation of Isotopically Labeled C Moieties Derived from Carbon Dioxide into Organic Molecules.

The conversion of carbon dioxide to formaldehyde is a transformation that is of considerable significance in view of the fact that formaldehyde is a widely used chemical, but this conversion is challenging because CO is resistant to chemical transformations. Therefore, we report here that formaldehyde can be readily obtained from CO at room temperature the bis(silyl)acetal, HC(OSiPh). Specifically, formaldehyde is released from HC(OSiPh) upon treatment with CsF at room temperature.

Electrophotocatalysis with a Trisaminocyclopropenium Radical Dication.

Visible-light photocatalysis and electrocatalysis are two powerful strategies for the promotion of chemical reactions. Here, these two modalities are combined in an electrophotocatalytic oxidation platform. This chemistry employs a trisaminocyclopropenium (TAC) ion catalyst, which is electrochemically oxidized to form a cyclopropenium radical dication intermediate.

Oxidizable Ketones: Persistent Radical Cations from the Single-Electron Oxidation of 2,3-Diaminocyclopropenones.

Single electron oxidation of 2,3-diaminocyclopropenones is shown to give rise to stable diaminocyclopropenium oxyl (DACO) radical cations. Cyclic voltammetry reveals reversible oxidations in the range of +0.70-1.

Synthesis and Evaluation of Macrocyclic Peptide Aldehydes as Potent and Selective Inhibitors of the 20S Proteasome.

This research explores the first design and synthesis of macrocyclic peptide aldehydes as potent inhibitors of the 20S proteasome. Two novel macrocyclic peptide aldehydes based on the ring-size of the macrocyclic natural product TMC-95 were prepared and evaluated as inhibitors of the 20S proteasome. Both compounds inhibited in the low nanomolar range and proved to be selective for the proteasome over other serine and cysteine proteases, particularly when compared to linear analogues with similar amino acid sequences.