10.1021/jo00226a045
The research focuses on the synthesis of monocrotaline, a macrocyclic dilactone pyrrolizidine alkaloid, which is notable for its potent hepatotoxic and antitumor activity, as well as its role as a defensive agent and pheromone precursor in Danaid butterflies. The study addresses the challenges in synthesizing the 11-membered derivative monocrotaline, particularly its tendency for y-lactone formation, which complicates synthetic strategies. The researchers developed a sequence involving the coupling of compounds 10 and 6, followed by nucleophilic ring closure, which includes the displacement of mesylate by a carboxylate ion generated in situ through the desilylation of a β-(trimethylsilyl)ethyl ester 3. Key chemicals used in the process include retronecine derivatives, glutaric anhydride derivative 5, 2-(trimethylsilyl)ethanol, and various reagents for cyclization and deprotection steps. The conclusions of the research confirm the generality of the nucleophilic cyclization method for the synthesis of retronecine-derived dilactones and provide a complete synthesis of monocrotaline, highlighting the effectiveness of the method in the case of pyrrolizidine alkaloids.
