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

Org Lett. 2015 Feb 6;17(3):492-5. doi: 10.1021/ol503507g. Epub 2015 Jan 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Depsipeptides / chemical synthesis*
  • Depsipeptides / chemistry
  • Depsipeptides / pharmacology*
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology
  • Platelet Aggregation Inhibitors / chemical synthesis*
  • Platelet Aggregation Inhibitors / chemistry
  • Platelet Aggregation Inhibitors / pharmacology*

Substances

  • Depsipeptides
  • Peptides, Cyclic
  • Platelet Aggregation Inhibitors
  • YM-254890
  • YM-280193