Absolute configuration assignment of (+)‐fluralaner using vibrational circular dichroism. Issue 12 (5th October 2017)

• Record Type: Journal Article
• Authors: Kong, John; Joyce, Leo A.; Liu, Jinchu; Jarrell, Tiffany M.; Culberson, J. Chris; Sherer, Edward C.
• Is Part Of: Chirality. Volume 29:Issue 12(2017)
• Page Start: 854
• Page End: 864
• Publication Date: 2017-10-05
• Subjects: absolute configuration -- Bravecto -- DFT -- fluralaner -- VCD -- vibrational circular dichroism; Chirality -- Periodicals; Pharmaceutical chemistry -- Periodicals; 541.22
• DOI: 10.1002/chir.22770
• Languages: English
• ISSNs: 0899-0042

Abstract

Abstract: The absolute configurations of the separated enantiomers of fluralaner, a racemic animal health product used to prevent fleas and ticks, have been assigned using vibrational circular dichroism (VCD). The crystallographic structure of the active enantiomer (+)‐fluralaner has previously been shown to have the ( S ) configuration using small molecule crystallography. We sought a faster analytical method to determine the absolute configuration of the separated enantiomers. When comparing the measured IR (infrared) and VCD spectra, it is apparent that the amide carbonyl groups appear in the IR but are nearly absent in the VCD. Computational work to calculate the VCD and IR using in vacuo models, implicit solvation, and explicitly solvated complexes has implicated conformational averaging of the carbonyl VCD intensities. Abstract :