Antiviral Activities of Halogenated Emodin Derivatives against Human Coronavirus NL63.

The current COVID-19 outbreak has highlighted the need for the development of new vaccines and drugs to combat Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Recently, various drugs have been proposed as potentially effective against COVID-19, such as remdesivir, infliximab and imatinib. Natural plants have been used as an alternative source of drugs for thousands of years, and some of them are effective for the treatment of various viral diseases. Emodin (1,3,8-trihydroxy-6-methylanthracene-9,10-dione) is a biologically active anthraquinone with antiviral activity that is found in various plants. We studied the selectivity of electrophilic aromatic substitution reactions on an emodin core (halogenation, nitration and sulfonation), which resulted in a library of emodin derivatives. The main aim of this work was to carry out an initial evaluation of the potential to improve the activity of emodin against human coronavirus NL63 (HCoV-NL63) and also to generate a set of initial SAR guidelines. We have prepared emodin derivatives which displayed significant anti-HCoV-NL63 activity. We observed that halogenation of emodin can improve its antiviral activity. The most active compound in this study was the iodinated emodin analogue E_3I, whose anti-HCoV-NL63 activity was comparable to that of remdesivir. Evaluation of the emodin analogues also revealed some unwanted toxicity to Vero cells. Since new synthetic routes are now available that allow modification of the emodin structure, it is reasonable to expect that analogues with significantly improved anti-HCoV-NL63 activity and lowered toxicity may thus be generated.

One pot synthesis of trifluoromethyl aryl sulfoxides by trifluoromethylthiolation of arenes and subsequent oxidation with hydrogen peroxide.

Hydrogen peroxide was used for oxidation of various aryl trifluoromethyl sulfides. Trifluoroacetic acid was used as an activating solvent that enables non-catalyzed oxidation and increases selectivity for sulfoxide formation. As shown by oxidation of thianthrene TFA enhances electrophilic character of the oxidant and further oxidation of sulfoxide group is blocked. We have joined trifluoromethylthiolation of arenes using a modified Billard reagent (p-ClPhNHSCF3) with oxidation of aryl trifluoromethyl sulfides using 1.2 equiv. of 30% aqueous hydrogen peroxide and this one-pot process has superior yields than would have been obtained in a two step process.