β-Lactams as building blocks in the synthesis of macrocyclic spermine and spermidine alkaloids

Syntheses of the macrocyclic spermidine alkaloids (±)-celacinnine () and (±)-dihydroperiphylline () as well as the related spermine alkaloid (±)-verbascenine () were accomplished by means of sequential ring expansions of smaller lactam rings. Three ring expansion methods were employed: (1) transamidation of N-(aminoalkyl)lactams, (2) β-lactam-lactim ether condensation followed by reductive cleavage of the bicyclic 4-oxotetrahydropyrimidine product with NaBH3CN/AcOH and (3) bicyclic acyl hydrazine formation followed by N–N bond cleavage with Na/NH3. Each synthesis features ring expansion of a 4-phenylazetidin-2-one intermediate that undergoes transamidative ring expansion or lactim ether condensation.