Resolving Entangled JH-H-Coupling Patterns for Steroidal Structure Determinations by NMR Spectroscopy

Abstract

For decades, high-resolution 1H NMR spectroscopy has been routinely utilized to analyze both naturally occurring steroid hormones and synthetic steroids, which play important roles in regulating physiological functions in humans. Because the 1H signals are inevitably superimposed and entangled with various JH–H splitting patterns, such that the individual 1H chemical shift and associated JH–H coupling identities are hardly resolved. Given this, applications of thess information for elucidating steroidal molecular structures and steroid/ligand interactions at the atomic level were largely restricted. To overcome, we devoted to unraveling the entangled JH–H splitting patterns of two similar steroidal compounds having fully unsaturated protons, i.e., androstanolone and epiandrosterone (denoted as 1 and 2, respectively), in which only hydroxyl and ketone substituents attached to C3 and C17 were interchanged. Here we demonstrated that the JH–H values deduced from 1 and 2 are universal and applicable to other steroids, such as testosterone, 3β, 21-dihydroxygregna-5-en-20-one, prednisolone, and estradiol. On the other hand, the 1H chemical shifts may deviate substantially from sample to sample. In this communication, we propose a simple but novel scheme for resolving the complicate JH–H splitting patterns and 1H chemical shifts, aiming for steroidal structure determinations.

Essential Terminology Connects NMR and qNMR Spectroscopy to Its Theoretical Foundation

“…Ignoring such specific information inevitably leads to misleading and/or erroneous assignments and quantitative evaluations when doing qNMR. The raw NMR data (FID) for this case study was kindly shared by the authors of [21] at DOI:10.7910/DVN/MOCHRD.…”

Essential Terminology Connects NMR and qNMR Spectroscopy to Its Theoretical Foundation

“…Ignoring such specific information inevitably leads to misleading and/or erroneous assignments and quantitative evaluations when doing qNMR. The raw NMR data (FID) for this case study was kindly shared by the authors of [21] at DOI:10.7910/DVN/MOCHRD. Observed NMR Spectra, see [22,23] and references therein), there is a general belief that this type of analysis is limited to 8-12 spins and not useful as a general application.…”