Homaline, isolated from the leaves of Homalium pronyense, has a structure incorporating the naturally occurring polyamine, spermine, along with two cinnamic acid residues. At the time of its isolation, the bis-eight-membered lactam system was unique among natural products, although three related alkaloids have since been found.

Studies by Wasserman and Hlasta related to the synthesis of 3-aminonocardicinic acid suggested that this compound, containing (beta)-phenyl-(beta)-aminopropionamide residues, might be readily constituted by transamidation of a suitable bis-(beta)-lactam precursor. (beta)-Lactams are remarkably stable to hydrolysis considering the strain in the four-membered ring. They do, however, undergo ready ring opening when subjected to intramolecular attack by nucleophiles through a favorable transition state. It therefore appeared likely that intramolecular aminolysis of a suitably functionalized (beta)-lactam precursor could lead to desdimethylhomaline, dimethylation of which would give the natural product. Herein, an absolute asymmetric synthesis of homaline is described proceeding from the known N,N'-bis-(3-hydroxypropyl)-1,4-diaminobutane and (-)-4-phenyl-2-azetidinone.