Prioritizing natural product compounds using 1D-TOCSY NMR spectroscopy

Area of Science:

• Natural Product Chemistry
• Drug Discovery
• Spectroscopy

Background:

• Natural products (NPs) are crucial for pharmaceuticals, but drug discovery faces challenges like re-isolating known compounds.
• Liquid chromatography coupled mass spectrometry (LC-MS) is a common dereplication tool but cannot differentiate isomers or detect all metabolites.
• Complementary techniques are needed to enhance the identification of known and novel bioactive compounds.

Purpose of the Study:

• To develop and apply a novel one-dimensional TOCSY-based dereplication method for natural product research.
• To efficiently identify and remove known non-bioactive triterpenoids from lichen extracts.
• To facilitate the discovery of new, potentially cytotoxic compounds from the lichen *Niebla homalea*.

Main Methods:

• Utilized one-dimensional Total Correlation Spectroscopy (TOCSY) NMR for dereplication.
• Employed LC-MS for initial compound analysis and separation.
• Isolated and characterized new triterpenoids from *Niebla homalea*.

Main Results:

• Developed a TOCSY-based method to rapidly identify known triterpenoids, including isomers.
• Successfully differentiated known non-cytotoxic triterpenoids from potentially bioactive fractions.
• Isolated five new and three known triterpenoids from *Niebla homalea*, and a new compound (11) from another *Niebla* species.

Conclusions:

• One-dimensional TOCSY NMR is a powerful, complementary tool for natural product dereplication, overcoming limitations of LC-MS.
• This method accelerates the identification of known compounds, enabling a focused search for novel bioactive molecules.
• The approach aids in prioritizing fractions for the discovery of new chemical entities with therapeutic potential.