Metal-Free Direct Amidation of Naphthoquinones Using Hydroxamic Acids as an Amide Source: Application in the Synthesis of an HDAC6 Inhibitor

Org Lett. 2016 Nov 4;18(21):5512-5515. doi: 10.1021/acs.orglett.6b02740. Epub 2016 Oct 19.

Abstract

A novel synthetic approach to amidoquinones by the reaction of naphthoquinones with hydroxamic acids under basic conditions was developed. The reaction is mild and operationally simple, and it affords high yields of amidoquinones. With this new method, a novel, very strong HDAC6 inhibitor, which showed high toxicity to AML cells, was successfully synthesized.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology*
  • Dose-Response Relationship, Drug
  • Histone Deacetylase 6 / antagonists & inhibitors*
  • Histone Deacetylase 6 / metabolism
  • Histone Deacetylase Inhibitors / chemical synthesis
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Hydroxamic Acids / chemistry*
  • Molecular Structure
  • Naphthoquinones / chemistry*
  • Recombinant Proteins / metabolism
  • Structure-Activity Relationship

Substances

  • Amides
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Naphthoquinones
  • Recombinant Proteins
  • HDAC6 protein, human
  • Histone Deacetylase 6