title: Total synthesis of the cyclic depsipeptide YM-280193, a platelet aggregation inhibitor.
abstract: 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.
authors.affiliation: School of Biological Sciences, Maurice Wilkins Centre for Molecular Biodiscovery and School of Chemical Sciences, The University of Auckland , 23 Symonds Street, Auckland 1142, New Zealand.
authors.forename: Harveen
authors.initials: H
authors.lastname: Kaur
authors.forename: Paul W R
authors.initials: PW
authors.lastname: Harris
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Little
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Brimble
mesh_terms: D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D047630:Depsipeptides; D010456:Peptides, Cyclic; D010975:Platelet Aggregation Inhibitors; C475455:YM-254890; C000596455:YM-280193