Chiral analysis of pantolactone with molecular rotational resonance spectroscopy

Abstract

A molecular rotational resonance spectroscopy method for measuring the enantiomeric excess of pantolactone, an intermediate in the synthesis of panthenol and pantothenic acid, is presented. The enantiomers are distinguished via complexation with a small chiral tag molecule, which produces diastereomeric complexes in the pulsed jet expansion used to inject the sample into the spectrometer. These complexes have distinct moments of inertia, so their spectra are resolved by MRR spectroscopy. Quantitative enantiomeric excess (EE) measurements are made by taking the ratio of normalized complex signal levels when a chiral tag sample of high, known EE is used, while the absolute configuration of the sample can be determined from electronic structure calculations of the complex geometries. These measurements can be performed without the need for reference samples with known enantiopurity. Two instruments were used in the analysis. A broadband, chirped-pulse spectrometer is used to perform structural characterization of the complexes. The broadband spectrometer is also used to determine the EE; however, this approach requires relatively long measurement times. A targeted MRR spectrometer is also used to demonstrate EE analysis with approximately 15-min sample-to-sample cycle time. The quantitative accuracy of the method is demonstrated by comparison with chiral gas chromatography and through the measurement of a series of reference samples prepared from mixtures of (R)pantolactone and (S)-pantolactone samples of known EE.

Enantioselective Synthesis of Enantioisotopomers with Quantitative Chiral Analysis by Chiral Tag Rotational Spectroscopy

“…The features of rotational spectroscopy and their utility in the analysis of the isotopologue and isotopomer composition of reaction mixtures of deuterated molecules, including the potential for high‐throughput analysis, have been discussed in recent work [34, 35] . The limitation that enantiomers of an isotopically chiral molecule have identical rotational spectra is addressed by employing the recently introduced chiral analysis method of chiral tag rotational spectroscopy [36–38] …”

Enantioselective Synthesis of Enantioisotopomers with Quantitative Chiral Analysis by Chiral Tag Rotational Spectroscopy

“…The enantiomeric excess for ethylbenzene‐ d1 is obtained from the ratio of the transition intensities for homochiral and heterochiral complexes. This method has been presented previously and so is only briefly described here [36, 38] . The measurement uses transition intensities from the spectrum acquired using the racemic tag sample to correct for the instrument response.…”

“…This method has been presented previously and so is only briefly described here. [36,38] The measurement uses transition intensities from the spectrum acquired using the racemic tag sample to correct for the instrument response. The normalized transition intensities in the homochiral spectrum are defined as:…”

“…[34,35] The limitation that enantiomers of an isotopically chiral molecule have identical rotational spectra is addressed by employing the recently introduced chiral analysis method of chiral tag rotational spectroscopy. [36][37][38]…”

Trendbericht Analytische Chemie 2022

“…73)Weitere Herausforderungen und TrendsBesondere Aufmerksamkeit verdienen neue Ansätze zur Non-Targetund Spurenanalytik in (Ab-)Wässern, physiologischen Medien (Blut, Plasma, Urin) oder Fermentationsproben. Eine methodische Innovation in der Strukturaufklärung komplexer Gemische ist die MRR-Spektroskopie (molecular rotational resonance spectroscopy), mit der sich Enantiomere, Diastereomere und Verunreinigungen in flüchtigen Gemischen bestimmen lassen und die komplementäre Strukturinformationen zu IR, MS und NMR liefert 74).…”