Absolute configuration assignment of (+)-fluralaner using vibrational circular dichroism.

Area of Science:

• Analytical Chemistry
• Spectroscopy
• Organic Chemistry

Background:

• Fluralaner is a racemic animal health product crucial for flea and tick prevention.
• The (S) configuration of (+)-fluralaner was previously established using small molecule crystallography.
• A need exists for faster analytical methods to determine enantiomeric absolute configurations.

Purpose of the Study:

• To assign the absolute configurations of separated fluralaner enantiomers using Vibrational Circular Dichroism (VCD).
• To establish VCD as a rapid analytical alternative to crystallography for determining fluralaner's absolute configuration.
• To investigate spectral discrepancies between IR and VCD for fluralaner's amide carbonyl groups.

Main Methods:

• Separation of fluralaner enantiomers.
• Measurement of Infrared (IR) and Vibrational Circular Dichroism (VCD) spectra.
• Computational modeling of VCD and IR spectra using various solvation models (in vacuo, implicit, explicit).

Main Results:

• VCD successfully assigned the absolute configurations of fluralaner enantiomers.
• Amide carbonyl groups showed distinct spectral behavior: present in IR, nearly absent in VCD.
• Computational analysis suggested conformational averaging influences carbonyl VCD intensities.

Conclusions:

• VCD provides a faster and effective method for absolute configuration assignment of fluralaner.
• The study highlights the utility of VCD in analyzing complex molecules like fluralaner.
• Understanding spectral characteristics, such as carbonyl VCD behavior, is crucial for accurate enantiomeric analysis.