Targeting protein homeostasis with small molecules as a strategy for the development of pan-coronavirus antiviral therapies.

The COVID-19 pandemic has created a global health crisis, with challenges arising from the ongoing evolution of the SARS-CoV-2 virus, the emergence of new strains, and the long-term effects of COVID-19. Aiming to overcome the development of viral resistance, our study here focused on developing broad-spectrum pan-coronavirus antiviral therapies by targeting host protein quality control mechanisms essential for viral replication. Screening an in-house compound library led to the discovery of three candidate compounds targeting cellular proteostasis.

DPCD is a regulator of R2TP in ciliogenesis initiation through Akt signaling.

R2TP is a chaperone complex consisting of the AAA+ ATPases RUVBL1 and RUVBL2, as well as RPAP3 and PIH1D1 proteins. R2TP is responsible for the assembly of macromolecular complexes mainly acting through different adaptors. Using proximity-labeling mass spectrometry, we identified deleted in primary ciliary dyskinesia (DPCD) as an adaptor of R2TP.

4D-printed hybrids with localized shape memory behaviour: Implementation in a functionally graded structure.

4D-printed materials are an emerging field of research because the physical structure of these novel materials respond to environmental changes. 3D printing techniques have been employed to print a base material with shape memory properties. Geometrical deformations can be observed once an external stimulus triggers the shape memory effect (SME) integrated into the material.

Photocatalytic 1,1-Hydrofluoroalkylation of Alkynes with a Concurrent Vicinal Acylation: An Access to Fluoroalkylated Cyclic Ketones.

A visible-light-induced 1,1-hydrofluoroalkylation of alkynes with a concomitant vicinal acylation is developed using tetrahydrofuran (THF) as the hydrogen atom source. Various fluoroalkylated cyclic ketones, such as indanones, chroman-4-ones, 2,3-dihydroquinolin-4(1 H)-ones, and 3,4-dihydronaphthalen-1(2 H)-ones, can be efficiently synthesized with excellent trans-diastereoselectivity. The reaction represents the first example of 1,1-hydrofluoroalkylation of alkynes, thus providing a novel method for the construction of fluoroalkanes.

Palladium-catalyzed tandem cyclization/sulfonylation of homoallenyl amides with sodium sulfinates.

A palladium-catalyzed cyclizative sulfonylation of homoallenyl amides using sodium sulfinates as the sulfonylation reagent and PhI(OCCF) as the oxidant has been realized. The reaction proceeds at room temperature and produces structurally diverse 2-amino-5-sulfonylmethylfurans in good to excellent yields. A Pd(ii)/Pd(iv) catalytic cycle has been proposed for the formation of sulfonylated furans.

Visible-Light-Induced Tandem Radical Addition-Cyclization of Alkenyl Aldehydes Leading to Indanones and Related Compounds.

Herein we describe a novel, visible light-induced tandem radical addition-cyclization of alkenyl aldehydes with α-bromocarbonyl compounds. A set of cyclic ketones, including indanones, cyclopentenones, 3,4-dihydronaphthalen-1(2H)-ones, and chroman-4-ones, are synthesized at room temperature with high efficiency and good functional group compatibility. It represents the first report on the catalytic 1,2-acylalkylation of unactivated alkenes.

Copper-catalyzed cascade annulation between α-bromocarbonyls and biaryl or (Z)-arylvinylacetylenes enabling a direct synthesis of dibenzocycloheptanes and related compounds.

Copper-catalyzed cascade annulation of γ,δ-unsaturated α-bromocarbonyls with biaryl or (Z)-arylvinylacetylenes is presented, giving an expeditious access to dibenzocycloheptanes and related compounds in moderate to high yields. It provides a novel method for the one-pot synthesis of cycloheptane and cycloheptene-fused polycyclic scaffolds featuring a rare 7-endo-trig radical cyclization.