Alkaloid Synthesis via Intramolecular Ene Reaction. 2. Application to dl-Mesembrine and dl-Dihydromaritidine

Article abstract of DOI:10.1021/jo00346a028

The total syntheses of mesembrine (2) and dihydromaritidine (3), alkaloids of the genera Sceletium and Amaryllis (respectively), are decscribed.The key strategy in each case involves the intramolecular ene cyclization of an appropriately constructed acylnitroso olefin, giving cyclic hydroxamic acid ("ene product") 12.Reduction of the hydroxamic acid to the lactam 4 is followed by N-methylation and hydroxylation at position C-6 via bromohydrin 15, introducing the oxygen functionality present in 2.Removal of bromine, oxidation of the alcohol to the keto lactam 13, andreductive removal of the lactam carbonyl gave racemic mesembrine.Removal of bromine from bromohydrin 20, obtained from lactam 4, followed by reduction with lithium aluminum hydride and Pictet-Spengler cyclization gave dihydromaritidine (3).