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Total Synthesis of the Cyclic Depsipeptide YM-280193, a Platelet Aggregation Inhibitor

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journal contribution
posted on 17.12.2015, 07:14 by Harveen Kaur, Paul W. R. Harris, Peter J. Little, Margaret A. Brimble
The first total synthesis of YM-280193, a cyclic depsipeptide that inhibits the ADP-induced aggregation of human platelets, is described. The monomer and dipeptide fragments were prepared using conventional chemistry and subsequently assembled by Fmoc-solid-phase peptide synthesis (Fmoc-SPPS). A late-stage novel bis-alkylation–elimination of cysteine on-resin was employed to introduce the unnatural N-methyldehydroalanine moiety. The final step involved execution of a key macrolactamization reaction between the hindered unnatural N,O-dimethylthreonine and β-hydroxyleucine residues.