Abstract
The α-fluorophosphonocarboxylate analogs of bisphosphonates have recently received attention due to their activity against Rab geranylgeranyl transferase, an enzyme implicated in a number of disease conditions. Most of the NMR data reported in the literature describing dialkyl α-fluorophosphonates are defined as first-order spectra. Here, we report a second-order pattern observed in 19F NMR spectrum, being a part of heteronuclear ABMX spin system. Such a spin system, CH2C(F)P, was subjected to NMR analysis supported by iteration.
GRAPHICAL ABSTRACT
Notes
Recently, a novel method of JHF determination, utilizing 2D-TOCSY technique, was described by Espinosa,4 extending the toolkit of the methods thus far applied, and overcoming the necessity of using spectrometer with two NMR probes.
Only when considering two small coupling constants (1.1 Hz), the spectrum could be iterated properly.
ABXY system for α-fluorophosphonocarboxylates has been reported previously only by Odinets et al.14 Authors described the 19F NMR spectrum as ddd, with the following parameters, determined for seven compounds (ranges are quoted): ΔvH = 0.24–0.26 ppm, 2JHH 15.8–16.0 Hz, 3JFH 11.4–13.2 and 38.5–39.0 Hz, 3JPH 8.0–12.6 and 4.0–6.0 Hz, 2JPF 82.6–83.4 Hz.
On acquiring higher resolution spectra, we found peaks of small integration next to 12 lines representing ABMX system. We suppose they might result from 19F–13C couplings through 1, 2, and 3 bonds. Such hypothesis is additionally supported by small variations of peak integrations between experimental and iterated (without taking into account this coupling) spectra.