Molnupiravir (MK-4482, EIDD-2801) is an experimental drug that has been demonstrated to be effective for the treatment of COVID-19 in human clinical trials. Herein, we report a concise synthesis of the drug via a novel thionated derivative that relies on one-pot methodologies, thus decreasing the number of purification steps required. This route provides the drug in an overall 62% yield and >99% purity and uses cheap and readily available bulk chemicals, thereby providing an affordable synthesis of the drug for cheaper and wider global accessibility.

Amino sugars, d-galactosamine (2-deoxy-2-aminogalactose), d-allosamine (2-deoxy-2-aminoallose) and d-gulosamine (2-deoxy-2-aminogulose) are components of several important carbohydrates of biologically relevant systems and in the area of therapeutics. In this work, we report the syntheses of their orthogonally protected N-phthalimido thioglycoside derivatives from d-glucosamine as building blocks for potential applications in further syntheses of their complex carbohydrates. The syntheses rely on installing orthogonal protections on N-pthalimido glucosamine thioglycoside followed by Lattrell-Dax inversions at C4 or C3, via the triflates, to yield d-galactosamine or d-allosamine, each of which is then readily converted to the d-gulosamine derivative by inversions at either C3 of the former or C4 of the latter. The utility of the synthesized building blocks is also demonstrated by the stereoselective and exclusive synthesis of the β-disaccharide in a proof of concept glycosylation reaction.

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