DFT calculation-assisted stereo-structural assignment of arundifungin

Area of Science:

• Organic Chemistry
• Computational Chemistry
• Mycology

Background:

• Arundifungin is a known potent antifungal agent against Candida and Aspergillus species.
• Previous research had only determined the planar structure of arundifungin.

Purpose of the Study:

• To elucidate the complete relative and absolute configuration of arundifungin.
• To investigate the structural contribution to antifungal activity by synthesizing and analyzing a related compound.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy for relative configuration assignment.
• Density Functional Theory (DFT) calculations for NMR chemical shifts and conformational analysis.
• Electronic Circular Dichroism (ECD) spectroscopy and Cotton effect analysis for absolute configuration.
• Chemical derivatization (modified Mosher's method) for side-chain configuration.

Main Results:

• The complete relative and absolute stereochemistry of arundifungin was established.
• 26-deoxyarundifungin was synthesized and its structure elucidated through spectral comparison.
• The hydroxyl group at C-26 was found to moderately contribute to antifungal activity.

Conclusions:

• The detailed structural elucidation of arundifungin provides a foundation for understanding its mechanism of action.
• The findings on 26-deoxyarundifungin highlight the importance of specific functional groups for antifungal potency.