Synthesis of 2-amino-8-oxodecanoic acids (Aodas) present in natural hystone deacetylase inhibitors

J Org Chem. 2006 Jan 6;71(1):103-7. doi: 10.1021/jo0518250.

Abstract

[reaction: see text] Differently substituted 2-amino-8-oxodecanoic acids (Aodas), present in naturally occurring inhibitors of hystone deacetylase (HDAC), have been prepared using a convergent approach. The configuration in position 2 was derived from enantiomerically pure allylglycine or glutamic acid, whereas the stereochemistry of the substituent in position 9 derived from lactic acid or glyceraldehyde derivatives. Starting from allylglycine, (S)-Aodas, protected at the nitrogen as Boc or Fmoc, were obtained in four steps in about 30% overall yield. These products have been used to prepare a simplified analogue of a natural cyclic tetrapeptide HDAC inhibitor by SPPS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amination
  • Decanoic Acids / chemical synthesis
  • Decanoic Acids / chemistry*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors*
  • Molecular Structure
  • Oxygen / chemistry*
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / pharmacology

Substances

  • Decanoic Acids
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Peptides
  • decanoic acid
  • Oxygen