Alternative methodologies in the synthesis of intubation drugs and Molnupiravir applying green and circular chemistry principles

Abstract

This proposal aims the development of alternative methodologies for the synthesis of some drugs used in the orotracheal (or endotracheal) intubation process. The intubation technique is critical in the context of the treatment of COVID-19 and requires the administration of several sedatives and neuromuscular blockers that must be administered before and during the procedure. During the second wave that occurred in Brazil (first quarter, 2021), shortage of intubation drugs was reported. In order to show an academic contribution against the COVID-19 pandemic, we initially selected two sedatives for study. Propofol and Etomidate. Based on the principles of circular and green chemistry, we propose alternative synthetic routes that are potentially adaptable to industry. In the simplest case of propofol, we will check the possibility of reuse (circular chemistry) of paracetamol as a possible precursor. In our group, we have already obtained etomidate in two steps. However, more efficient and greener conditions for the Mitsunobu reaction need to be improved. The antiviral Molnupiravir can be the first approved drug against COVID-19. Despite the synthetic routes are robust, we propose a systematic study regarding the synthesis of cytidine and a further investigation on the regioselective acetylation by lipases. We hope to obtain alternative routes, arouse the interest of academia and industry alike, mainly by applying greener and, if possible, sustainable principles. More details about the synthetic proposals are detailed throughout this proposal. (AU)