The Chemical Synthesis of Certain Therapeutically Significant Alkaloids in the Era of Sustainability

This perspective details work undertaken within the authors' laboratories that attempts to address at least some of the challenges associated with the development of industrially applicable total syntheses of the therapeutically significant alkaloids morphine, codeine, colchicine and galanthamine. A primary motivation for doing this derives from the significant threats emerging from the ongoing reliance on the natural sources (viz. plants) of these crucial, clinically deployed medicines. Beyond the need to simply develop abbreviated syntheses of these natural products are the requirements that the routes involved are not just time-efficient but also atom-economical and, as much as possible, employ sustainably-derived substrates, "green" reagents (or no reagents at all) and solvents. Operating under such constraints is discussed, as is the need to generate new biomass-derived platform molecules, especially nitrogen-containing ones for which there are few truly global sources at the present time.