Total synthesis of the cyclic depsipeptide YM-280193, a platelet aggregation inhibitor.

Harveen Kaur, Paul W R Harris, Peter J Little, Margaret A Brimble

Organic letters 2015 Feb 6

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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.

Citation

Harveen Kaur, Paul W R Harris, Peter J Little, Margaret A Brimble. Total synthesis of the cyclic depsipeptide YM-280193, a platelet aggregation inhibitor. Organic letters. 2015 Feb 6;17(3):492-5