TOTAL SYNTHESIS OF THE LYCOPODIUM ALKALOIDS MAGELLANINE AND MAGELLANINONE BY 3-FOLD ANNULATION OF 2-CYCLOPENTENONE

A stereocontrolled synthesis of the complete diquinane-based framework of the two unusual Lycopodium alkaloids magellanine and magellaninone is reported. Michael-Michael ring annulation of the alpha,beta-unsaturated ketone 4 obtained by dehydration of 5a rapidly led to enedione 7, functional group manipulation within which gave rise to 11. Once oxidation to the cyclopentenone had been accomplished, the piperidine ring part structure was incorporated by an unprecedented sequence that ultimately allowed for installation of the requisite cis ring juncture through epimerization. With 17a available, oxidation levels were concisely adjusted with concomitant incorporation of a methyl group to produce magellaninone (2). To complete the route to magellanine (1), 2 was chemoselectively reduced and subjected to a Mitsunobu protocol.