Application of 13C-labeling and 13C-13C COSY NMR experiments in the structure determination of a microbial natural product

Arch Pharm Res. 2014 Aug;37(8):967-71. doi: 10.1007/s12272-013-0254-8. Epub 2013 Oct 11.

Abstract

The elucidation of the structures of complex natural products bearing many quaternary carbons remains challenging, even in this advanced spectroscopic era. (13)C-(13)C COSY NMR spectroscopy shows direct couplings between (13)C and (13)C, which comprise the backbone of a natural product. Thus, this type of experiment is particularly useful for natural products bearing consecutive quaternary carbons. However, the low sensitivity of (13)C-based NMR experiments, due to the low natural abundance of the (13)C nucleus, is problematic when applying these techniques. Our efforts in the (13)C labeling of a microbial natural product, cyclopiazonic acid (1), by feeding (13)C-labeled glucose to the fungal culture, enabled us to acquire (13)C-(13)C COSY NMR spectra on a milligram scale that clearly show the carbon backbone of the compound. This is the first application of (13)C-(13)C COSY NMR experiments for a natural product. The results suggest that (13)C-(13)C COSY NMR spectroscopy can be routinely used for the structure determination of microbial natural products by (13)C-enrichment of a compound with (13)C-glucose.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillus flavus / growth & development*
  • Biological Products / chemistry*
  • Biological Products / isolation & purification
  • Carbon Isotopes
  • Carbon-13 Magnetic Resonance Spectroscopy / methods*
  • Indoles / chemistry*
  • Indoles / isolation & purification
  • Isotope Labeling
  • Molecular Structure

Substances

  • Biological Products
  • Carbon Isotopes
  • Indoles
  • cyclopiazonic acid