Development of Ultrapure and Potent Tannic Acids as a Pan-coronal Antiviral Therapeutic.

The rampageous transmission of SARS-CoV-2 has been devastatingly impacting human life and public health since late 2019. The waves of pandemic events caused by distinct coronaviruses at present and over the past decades have prompted the need to develop broad-spectrum antiviral drugs against them. In this study, our Pentarlandir ultrapure and potent tannic acids (UPPTA) showed activities against two coronaviral strains, SARS-CoV-2 and HCoV-OC43, the earliest-known coronaviruses. The mode of inhibition of Pentarlandir UPPTA is likely to act on 3-chymotrypsin-like protease (3CLpro) to prevent viral replication, as supported by results of biochemical analysis, a 3CLpro assay, and a "gain-of-function" 3CLpro overexpressed cell-based method. Even in the 3CLpro overexpressed environment, Pentarlandir UPPTA remained its antiviral characteristic. Utilizing cell-based virucidal and cytotoxicity assays, the 50% effective concentrations (EC50) and 50% cytotoxicity concentration (CC50) of Pentarlandir UPPTA were determined to be ∼0.5 and 52.5 µM against SARS-CoV-2, while they were 1.3 and 205.9 µM against HCoV-OC43, respectively. In the pharmacokinetic studies, Pentarlandir UPPTA was distributable at a high level to the lung tissue with no accumulation in the body, although the distribution was affected by the food effect. With further investigation in toxicology, Pentarlandir UPPTA demonstrated an overall safe toxicology profile. Taking these findings together, Pentarlandir UPPTA is considered to be a safe and efficacious pancoronal antiviral drug candidate that has been advanced to clinical development.

An efficient synthesis of trisubstituted oxazoles via chemoselective O-acylations and intramolecular Wittig reactions.

Preparation of new types of trisubstituted oxazoles is realized via chemoselective O-acylations and intramolecular Wittig reactions with ester functionalities using in situ formed phosphorus ylides as key intermediates. A plausible reaction mechanism for this undiscovered chemistry is also proposed based on the existence of expected and rearranged isomeric oxazoles.

Enantioselective organocatalytic Michael addition of ketones to alkylidene malonates.

Organocatalysts bearing sulfide or sulfone functions (1a-d) were studied for the direct asymmetric Michael addition of ketones and alkylidene malonates. The organocatalyst (S)-2-((naphthalen-2-ylthio)methyl)pyrrolidine, bearing a pyrrolidine and a sulfide moiety, showed a very high catalytic activity in the absence of additives. The reaction condition is mild, and the Michael adducts were obtained in very good enantioselectivities (up to 96%), diastereoselectivities (up to 95:5), and chemical yields (up to 95%).

Enantioselective synthesis of substituted pyrans via amine-catalyzed Michael addition and subsequent enolization/cyclisation.

An organocatalytic construction of optically enriched substituted pyran derivatives via amine-catalyzed Michael addition and subsequent enolization/cyclisation has been described starting from electronically poor alkenes. Functionalized pyrans were obtained in high enantioselectivities (up to 96%) and good yields (up to 90%) having three contiguous chiral centers.