Total synthesis of azumamide A and azumamide E, evaluation as histone deacetylase inhibitors, and design of a more potent analogue

Org Lett. 2007 Mar 15;9(6):1105-8. doi: 10.1021/ol070046y. Epub 2007 Feb 21.

Abstract

The unprecedented diastereoselective Mannich reaction of a Z-allylsulfoximine was a key step in the total synthesis of the marine natural products azumamide A and E, and an unnatural analogue. Their relative potency as histone deacetylase inhibitors was evaluated and found to correlate with predicted zinc-binding affinity. [reaction: see text]

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allyl Compounds / chemistry
  • Binding Sites
  • Biological Products / chemical synthesis
  • Biological Products / pharmacology
  • Dapsone / analogs & derivatives
  • Dapsone / chemistry
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors*
  • Models, Chemical
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / pharmacology
  • Stereoisomerism
  • Zinc / chemistry

Substances

  • Allyl Compounds
  • Biological Products
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Peptides, Cyclic
  • azumanide A
  • azumanide E
  • sulfoxone
  • Dapsone
  • Zinc