Can chemical synthesis help address issues related to the supply of therapeutically significant alkaloids in the era of sustainability?

Abstract A number of plant-derived alkaloids are deployed clinically for treating a range of ailments. Notable examples include morphine, codeine, galanthamine and colchicine. While the opium poppy-derived morphinan alkaloids are amongst the most widely prescribed drugs worldwide, today there remains a significant shortfall in legal access to these critical pain-relieving medicines for more than half of the world’s population. Exacerbating this disturbing situation are the impacts of climate change, habitat loss and the possibilities of crop losses (and even extinction) through disease (most particularly fungal infections), all of which threaten the supply chains for these crucial medicines. Herein we outline work undertaken within our laboratories that attempts to address the above-mentioned challenges through the development of concise, time-efficient, atom-economical and sustainably-oriented total syntheses of these clinically-deployed alkaloids. A necessary adjunct to such activities has been the need to develop new, potentially highly scalable and biomass-derived platform molecules, especially nitrogen-containing ones for which there are few examples at the present time.