Application of fluorine NMR for structure identification of steroids

Fluorinated steroids were examined using 1D and 2D homo- and heteronuclear F-19 NMR, such as F-19-H-1 and F-19-C-13. The utilization of fluorine NMR accounted for spectral simplification and resulted in a straight forward 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 F-19 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. F-19-H-1 HETCOR, F-19-C-13 HMQC and HMBC, and F-19-H-1 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 19F NMR to be a useful addition to the extensively used H-1 and C-13 NMR within structure elucidation and configuration determination of small molecules. Copyright (C) 2011 John Wiley & Sons, Ltd.