An oral non-covalent non-peptidic inhibitor of SARS-CoV-2 Mpro ameliorates viral replication and pathogenesis in vivo.

Safe, effective, and low-cost oral antiviral therapies are needed to treat those at high risk for developing severe COVID-19. To that end, we performed a high-throughput screen to identify non-peptidic, non-covalent inhibitors of the SARS-CoV-2 main protease (Mpro), an essential enzyme in viral replication. NZ-804 was developed from a screening hit through iterative rounds of structure-guided medicinal chemistry.

Chiral Teropyrenes: Synthesis, Structure, and Spectroscopic Studies.

We present the inaugural synthesis of a chiral teropyrene achieved through a four-fold alkyne benzannulation catalyzed by InCl, resulting in good yields. The product underwent thorough characterization using FT-Raman and FT-IR spectroscopies, demonstrating a close agreement with calculated spectra. X-ray crystallographic analysis unveiled a notable twist in the molecule's backbone, with an end-to-end twist angle of 51°, consistent with computational predictions.

Mild olefin formation bio-inspired vitamin B photocatalysis.

Dehydrohalogenation, or elimination of hydrogen-halide equivalents, remains one of the simplest methods for the installation of the biologically-important olefin functionality. However, this transformation often requires harsh, strongly-basic conditions, rare noble metals, or both, limiting its applicability in the synthesis of complex molecules. Nature has pursued a complementary approach in the novel vitamin B-dependent photoreceptor CarH, where photolysis of a cobalt-carbon bond leads to selective olefin formation under mild, physiologically-relevant conditions.

Four-Fold Alkyne Benzannulation: Synthesis, Properties, and Structure of Pyreno[]pyrene-Based Helicene Hybrids.

The synthesis of pyreno[]pyrene-based helicene hybrids was achieved in good yield via a four-fold alkyne benzannulation reaction that was promoted by Brønsted acid. The molecules are configurationally locked, allowing the enantiomers to be separated using chiral HPLC so that their photophysical and chiroptical properties, including circular dichroism and circularly polarized luminescence, could be studied.

Highly Regioselective Domino Benzannulation Reaction of Buta-1,3-diynes To Construct Irregular Nanographenes.

The properties of nanographenes can be tuned by changing their shapes, therefore the development of new methods suitable for the synthesis of various nanographenes is highly desirable. Described herein is an intramolecular InCl /AgNTf -catalyzed regioselective domino benzannulation reaction of buta-1,3-diynes to build irregular nanographenes. Different nanographene compounds were easily obtained in moderate to high yields through careful design of the precursor compounds.

One-Pot Domino Friedel-Crafts Acylation/Annulation between Alkynes and 2-Methoxybenzoyl Chlorides: Synthesis of 2,3-Disubstituted Chromen-4-one Derivatives.

A highly regioselective synthesis of 2,3-disubstituted chromen-4-one derivatives is accomplished from readily available internal alkynes and 2-methoxybenzoyl chlorides. The reaction proceeds via a domino intermolecular Friedel-Crafts acylation/intramolecular vinyl carbocation trapping (or oxa-Michael addition)/demethylation reaction sequence. This Lewis acid promoted method features relatively mild reaction conditions to synthesize a variety of 2,3-disubstituted chromen-4-one derivatives in one pot with up to 93% yield.