Avanços Recentes Na Síntese Do Remdesivir, Molnupiravir (Eidd-2801) E Tenofovir: Moléculas Promissoras No Tratamento Da Covid-19

Abstract

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.

Drug repositioning in the COVID-19 pandemic: fundamentals, synthetic routes, and overview of clinical studies

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Concise two-step chemical synthesis of molnupiravir

“…4 Due to the importance of this drug, there is a wide interest in developing an efficient and cost-effective synthesis route for its production to ensure a sufficient and readily available global supply chain. 5 In this context, there are many chemical routes already described to molnupiravir (2) from uridine (1) (Scheme 1). In 2019, the patented seminal work developed at Emory University involves a 5-step route to molnupiravir (2) with 17% overall yield aer purications by chromatography.…”

“… 4 Due to the importance of this drug, there is a wide interest in developing an efficient and cost-effective synthesis route for its production to ensure a sufficient and readily available global supply chain. 5 …”