A Condensed, Scalable Synthesis of Racemic Koningic Acid

J Org Chem. 2020 May 15;85(10):6788-6793. doi: 10.1021/acs.joc.0c00344. Epub 2020 May 4.

Abstract

The natural product koningic acid (KA) is a selective covalent inhibitor of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a critical node in the glycolysis pathway. While KA is available commercially, sources are limited and its cost becomes rapidly prohibitive beyond the milligram scale. Additionally, a practical and flexible synthetic route to KA and analogs remains to be developed. Here we detail a new route that is operationally safer, scalable and offers a five-step reduction in the previously reported longest linear sequence.

MeSH terms

  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • Sesquiterpenes*

Substances

  • Sesquiterpenes
  • heptelidic acid
  • Glyceraldehyde-3-Phosphate Dehydrogenases