Synthetic studies on the lycopodium alkaloids. IV. Total synthesis of dl-anhydrolycodoline and dl-lycopodine.

The total synthesis of dl-anhydrolycodoline is reported. The amino-ketone (3), obtained from the amine (4) in four steps, was treated with acrylyl chloride to give the amide (1). Unfortunately, the intramolecular Michael-type cyclization of 1 to the lactam (9) for lycodoline did not take place for a stereoelectronic reason. Dehydration of 1 with conc. sulfuric acid afforded the anhydro-amide (10), which was cyclized in the presence of sodium ethoxide and dicyclohexyl-18-crown-6 to give the tetracyclic lactam (11) in a moderate yield. Reduction of 11 with lithium aluminum hydride followed by oxidation with Jones reagent afforded dl-anhydrolycodoline.