Total Synthesis of Melicoptelines C-E: Antiviral Cyclopeptides Containing a Hexahydropyrrolo[2,3- b ]indole Moiety.

Melicoptelines, natural cyclopeptides containing a 3a-hydroxy hexahydropyrrolo[2,3- b ]indole (HPI) moiety, exhibit anti-influenza activity. Herein, we report the first total synthesis of melicoptelines C-E ( 1-3 , respectively). The core 3a-hydroxy HPIs were synthesized in a diastereoselective manner from l-tryptophan using dimethyldioxirane-mediated oxidation. Subsequently, sequential peptide couplings and cyclization completed the synthesis of melicoptelines C-E and unnatural melicopteline 4 . The synthesized melicoptelines were evaluated for their anti-influenza activity, and melicopteline E showed the most potent inhibition of cytopathic effects.