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. Copyright © 2011 John Wiley & Sons, Ltd.