Application of HFX NMR to Facilitate the Complete Assignment of the Anti-fungal Agent Voriconazole
Introduction
Fluorine is found with an ever-increasing frequency in materials science and both legal and illicit drugs [ref 1-5]. In this application note results are presented to illustrate the simplification afforded by the routine application of triple-resonance NMR to clearly assign voriconazole, a molecule containing proton, carbon, and nitrogen molecules with many atoms exhibiting J-coupling to fluorine. The HFX ROYAL probe is a completely new probe technology utilizing magnetic coupling to afford highly efficient HF-X tuning which can function as a simple switch to highest sensitivity dedicated 1H or 19F or very well balanced dual 1H/19F performance on demand. References 6-8 detail the technological developments for the HFX ROYAL probe.
The 1H NMR spectrum acquired at 500 MHz with the Royal HFX probe using the ECZR 500 console is presented in figure 2. Because of the nature of the structure there is at first glance very little fine structure to facilitate clear assignments. Almost all resonances including what appear to be singlets are significantly sharpened by the application of 19F decoupling. However, the top pane of figure 2 detailing the phenyl region which contains two 19F resonances cannot be visually assigned without 19F decoupling. Decoupling 19F removes confusion with the three resonances for Phe-6, PHe-3, and Phe-5 being revealed with classically simple ortho, ortho-meta, and meta coupling patterns respectively… cannot be visually assigned without 19F decoupling.