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

Syntheses of the macrocyclic spermidine alkaloids (+/-)-celacinnine (1) and (+/-)-dihydroperiphylline (2) as well as the related spermine alkaloid (+/-)-verbascenine (3) 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) beta-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. (C) 2002 Elsevier Science Ltd. All rights reserved.