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

Abstract

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. Subse-quently, 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. <comment>Superscript/Subscript Available</comment