Synthesis and DFT-NMR-guided structure revision of cremenolide

Area of Science:

• Natural Product Chemistry
• Computational Chemistry
• Organic Synthesis

Background:

• Nonenolides are a class of natural products with diverse biological activities.
• Cremenolide exhibits potential as an anti-plant pathogen and plant growth promoter.
• Accurate structural elucidation is crucial for understanding and utilizing bioactive compounds.

Purpose of the Study:

• To revise and unambiguously confirm the chemical structure of cremenolide.
• To establish the relative configuration of the nonenolide diastereomers.
• To validate the utility of DFT-based NMR calculations in natural product structure determination.

Main Methods:

• Re-analysis of reported Nuclear Magnetic Resonance (NMR) spectra.
• Density Functional Theory (DFT)-based computational NMR calculations using the ωB97X-D functional for all possible diastereomers.
• Chemical synthesis of the proposed cremenolide diastereomer for confirmation.

Main Results:

• The planar structure of cremenolide was re-evaluated based on spectral data.
• Computational NMR calculations predicted the relative configuration of cremenolide.
• Successful synthesis of the target diastereomer confirmed the computationally predicted structure.

Conclusions:

• The structure of cremenolide was successfully revised and its relative configuration unambiguously determined.
• The combination of DFT-based NMR calculations and targeted synthesis provides an efficient strategy for natural product structure elucidation.
• This study enhances our understanding of cremenolide's chemical properties and potential applications in agriculture.