Iodine-Mediated Alkoxyselenylation of Alkenes and Dienes with Elemental Selenium.

A one-pot synthesis of linear and cyclic ß-alkoxyselenides is developed through the iodine-mediated three-component reaction of elemental selenium with alkenes (dienes) and alcohols. Selenylation of 1,5-hexadiene gives 2,5-di(methoxymethyl)tetrahydroselenophene and 2-methoxy-6-(methoxymethyl)tetrahydro-2H-selenopyran via the 5-exo-trig and 6-endo-trig cyclization. 1,7-Octadiene affords only linear 1:2 adduct with two terminal double bonds. 1,5-Cyclooctadiene results in one diastereomer of 2,6-dialkoxy-9-selenabicyclo [3.3.1]nonanes via 6-exo-trig cyclization. With 1,3-diethenyl-1,1,3,3-tetramethyldisiloxane, the first ring-substituted representative of a very rare class of heterocycles, 1,4,2,6-oxaselenadisilinanes, was obtained at a high yield.

Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(E)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs.

A series of hitherto unknown (1,4-disubstituted-1,2,3-triazol)-(E)-2-methyl-but-2-enyl nucleosides phosphonate prodrugs bearing 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as the key synthetic step. All novel compounds were evaluated for their antiviral activities against HBV, HIV and SARS-CoV-2. Among these molecules, only compound 15j, a hexadecyloxypropyl (HDP)/(isopropyloxycarbonyl-oxymethyl)-ester (POC) prodrug, showed activity against HBV in Huh7 cell cultures with 62% inhibition at 10 µM, without significant cytotoxicity (IC50 = 66.4 µM in HepG2 cells, IC50 = 43.1 µM in HepG2 cells) at 10 µM.

Three salvianolic acids inhibit 2019-nCoV spike pseudovirus viropexis by binding to both its RBD and receptor ACE2.

Since December 2019, the new coronavirus (also known as severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2, 2019-nCoV])-induced disease, COVID-19, has spread rapidly worldwide. Studies have reported that the traditional Chinese medicine Salvia miltiorrhiza possesses remarkable antiviral properties; however, the anti-coronaviral activity of its main components, salvianolic acid A (SAA), salvianolic acid B (SAB), and salvianolic acid C (SAC) is still debated. In this study, we used Cell Counting Kit-8 staining and flow cytometry to evaluate the toxicity of SAA, SAB, and SAC on ACE2 (angiotensin-converting enzyme 2) high-expressing HEK293T cells (ACE2h cells). We found that SAA, SAB, and SAC had a minor effect on the viability of ACE2h cells at concentrations below 100 µM. We further evaluated the binding capacity of SAA, SAB, and SAC to ACE2 and the spike protein of 2019-nCoV using molecular docking and surface plasmon resonance. They could bind to the receptor-binding domain (RBD) of the 2019-nCoV with a binding constant (KD ) of (3.82 ± 0.43) e-6 M, (5.15 ± 0.64)e-7 M, and (2.19 ± 0.14)e-6 M; and bind to ACE2 with KD (4.08 ± 0.61)e-7 M, (2.95 ± 0.78)e-7 M, and (7.32 ± 0.42)e-7 M, respectively. As a result, SAA, SAB, and SAC were determined to inhibit the entry of 2019-nCoV Spike pseudovirus with an EC50 of 11.31, 6.22, and 10.14 µM on ACE2h cells, respectively. In conclusion, our study revealed that three Salvianolic acids can inhibit the entry of 2019-nCoV spike pseudovirus into ACE2h cells by binding to the RBD of the 2019-nCoV spike protein and ACE2 protein.

Nickel-Catalyzed Asymmetric Synthesis of α-Arylbenzamides.

A nickel-catalyzed asymmetric reductive hydroarylation of vinyl amides to produce enantioenriched α-arylbenzamides is reported. The use of a chiral bisimidazoline (BIm) ligand, in combination with diethoxymethylsilane and aryl halides, enables the regioselective introduction of aryl groups to the internal position of the olefin, forging a new stereogenic center α to the N atom. The use of neutral reagents and mild reaction conditions provides simple access to pharmacologically relevant motifs present in anticancer, SARS-CoV PLpro inhibitors, and KCNQ channel openers.