Total synthesis of syringolin A and B

Org Lett. 2010 May 21;12(10):2402-5. doi: 10.1021/ol100761z.

Abstract

Total syntheses of two recently discovered proteasome inhibitors, syringolin A and B, are reported. The key to our approach was creation of the alpha,beta-unsaturated 12-membered lactam via intramolecular Horner-Wadsworth-Emmons reaction. Such reactions have been broadly used to prepared macrolactones, but this work presents a rarer example of its application to macrolactams. The final steps involved attachment of the bis(valinyl)urea side chain using peptide coupling procedures, including a method based on the unprotected valine N-carboxy anhydride. The additional alkene of syringolin A was created through cross-metathesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Molecular Conformation
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / chemistry
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry
  • Proteasome Inhibitors
  • Stereoisomerism
  • Urea / analogs & derivatives*
  • Urea / chemical synthesis
  • Urea / chemistry

Substances

  • Peptides, Cyclic
  • Protease Inhibitors
  • Proteasome Inhibitors
  • syringolin A
  • syringolin B
  • Urea