Application of fluorine NMR for structure identification of steroids

Abstract

Fluorinated steroids were examined using 1D and 2D homo- and heteronuclear (19)F NMR, such as (19)F-(1) H and (19)F-(13)C. The utilization of fluorine NMR accounted for spectral simplification and resulted in a straightforward pathway for the determination of structures including the configuration of these compounds; these steroids present an illustrative example for other types of fluorinated compounds, which are increasingly encountered in drug discovery. The potential of (19)F NMR is elaborated on in detail for two compounds containing diastereotopic fluorines with different coupling patterns. The analysis of the coupling patterns and the through-space interactions resulted in the determination of the structure and configuration. Heteronuclear correlation experiments, i.e. (19)F-(1)H HETCOR, (19)F-(13)C HMQC and HMBC, and (19)F-(1)H HOESY, were applied to determine first the relative stereochemistry and then the molecular configuration at C4 and C5 of a steroidal compound bearing a fused three-membered ring with two fluorine substituents. These examples proved (19)F NMR to be a useful addition to the extensively used (1)H and (13)C NMR within structure elucidation and configuration determination of small molecules.

NMR spectral analysis of second-order 19F-19F, 19F-1H and 13C-19F coupling constants in pentafluorobenzene and tetrafluoro-4-(morpholino)pyridine using ANATOLIA

“…A detailed database of fluorine coupling constants was created by Emsley et al in 1976 [9], and specific interactions of 2 J 15 N- 19 F coupling in a fluoropyridine reported in 1979 [10], and a family of fluoropyridines in 1994 [11]. More recently fluorinated pharmaceuticals have renewed interest in fluorine NMR spectral analysis [12], and a book published in 2016 provides a detailed summary of 19 F NMR methods and literature to date [13].…”

An efficient DFT method of predicting the one-, two- and three-bond indirect spin–spin coupling constants involving a fluorine nucleus in fluoroalkanes

“…These features cause that uorine nucleus present in the molecule is a very convenient probe, useful in structural studies of uorocompounds. [5][6][7][8][9][10][11][12] Thus, the chemistry of uorinecontaining compounds is an important branch of chemistry and, simultaneously, NMR of such compounds is an interesting and important part of NMR spectroscopy.…”

The Antagonist Effect of Nitrogen Lone Pair: 3JHFversus5JHF

“…Although the vast majority of J‐coupling reported in the literature are related to 1 H‐ 1 H and 1 H‐ 13 C interactions, there are other magnetic nuclei, which are commonly found in organic molecules, and are able to exchange information with other nuclei via scalar coupling. This is the case of fluorine containing drugs, which are increasing very rapidly in the market ,…”