RECENT ADVANCES IN THE SYNTHESIS OF REMDESIVIR, MOLNUPIRAVIR (EIDD-2801) AND TENOFOVIR: PROMISING MOLECULES IN THE TREATMENT OF COVID-19. The search for new treatments to contain the Covid-19 pandemic has highlighted the importance of nucleoside antivirals, such as Remdesivir, Tenofovir and Molnupiravir. Over the last two years, these molecules have been intensely investigated as promising alternatives against SARS-CoV-2 virus. Considering the increasingly demand for those substances, several research groups are intensely investigating synthetic developments in order to obtain these nucleoside derivatives and their intermediates in a fast, efficient and accessible manner. In this context, this review aims to in-depth present the recent advances concerning the preparation of Remdesivir, Tenofovir and Molnupiravir. Aspects involving differences in the starting materials and reagents, as well as the advantages and limitations of each protocol would be carefully disclosed. Moreover, the use of synthetic tools, such as flow chemistry, organocatalysis and biocatalysis, would also be detailed. Finally, this review also presents aspects involving the scale-up of these transformations, including discussions about stereo- and diastereoselectivity, as well as product isolation details. In summary, an overview of the existing synthetic strategies for these active pharmaceutical ingredients (APIs) are presented.

The plant phenolic natural products (PNPs) protocatechuic aldehyde, syringaldehyde and vanillin were used as platforms for obtaining four urease inhibitors. Urea (urease substrate) or thiourea (urease inhibitor) core was added to the structure of newly synthesized compounds to provide inhibitors up to 230-fold more active than the PNPs they originated from. The PNP derivatives are mixed inhibitors with higher affinity to urease active site. Two compounds were as efficient as N-(butyl)thiophosphoric triamide (NBPT) toward soil. Overall, PNPs derivatives are promising urease inhibitors for use as additive in urea-based fertilizers formulations.