HiFSA Fingerprinting Applied to Isomers with Near-Identical NMR Spectra: The Silybin/Isosilybin Case

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Tyler Graf, Research Scientist (Creator)
Nicholas Oberlies, Patricia A. Sullivan Distinguished Professor of Chemistry (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/

Abstract: This study demonstrates how regio- and diastereo-isomers with near-identical NMR spectra can be distinguished and unambiguously assigned using quantum mechanical driven 1H iterative Full Spin Analysis (HiFSA). The method is illustrated with four natural products, the flavonolignans silybin A, silybin B, isosilybin A, and isosilybin B, which exhibit extremely similar coupling patterns and chemical shift differences well below the commonly reported level of accuracy of 0.01 ppm. The HiFSA approach generated highly reproducible 1H NMR fingerprints that enable distinction of all four isomers at 1H frequencies from 300 to 900 MHz. Furthermore, it is demonstrated that the underlying numeric 1H NMR profiles, combined with iterative computational analysis, allow parallel quantification of all four isomers, even in difficult to characterize reference materials and mixtures. The results shed new light on the historical challenges to the qualitative and quantitative analysis of these therapeutically relevant flavonolignans and open new opportunities to explore hidden diversity in the chemical space of organic molecules.

Additional Information

Publication
The Journal of Organic Chemistry, 78(7), 2827–2839
Language: English
Date: 2013
Keywords
Organic chemistry, Milk thistle, flavonolignans, silybin, HiFSA, NMR profiles

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