A novel hydrogen migration of dialkylphosphonic acid esters using electrospray ionization tandem mass spectrometry

Abstract

In this paper, attention is focused on analysis of the fragmentation of α-hydroxy-β-amino phosphonate esters designed as inhibitors of protein kinase A. An interesting proton migration mechanism in the cleavage of the P-C bond is investigated by electrospray ionization tandem mass spectrometry. A possible rearrangement mechanism is proposed and verified by high-resolution mass spectra using isotope deuterium/hydrogen-exchange technology and additionally checked by detailed DFT calculation based on Gaussian software. The result clearly indicates that this mechanism proceeds by a five-membered ring concerted transition state with activation energy 11.3 kcal mol(-1) for the compound 3f. The overall reaction is endothermic with an energy 13.2 kcal mol(-1). The effect of different substituents and different metal ions for rearrangement of these esters is studied by experiment and theory. It is concluded that this rearrangement process is energetically unfavorable and hence only occurs in the mass spectrometer.

Cleavage of phosphorus-carbon (P-C) bonds of α-amino phosphonates with intramolecular hydrogen migration in the gas phase using electrospray ionization tandem mass spectrometry

“…It was found that the fragmentation pathways of P–C bonds were different from those of phosphates and phosphoramidates containing P–O and P–N bonds, respectively . Several interesting rearrangement reactions have been observed, such as hydrogen‐atom migration from the hydroxyl to the phosphoryl group for α‐hydroxyl dialkylphosphonic acid esters, neutral phosphoryl amine loss from phosphonate peptides, and oxygen‐atom migration to phosphoryl groups for [(4‐substituted‐benzoylamino)phenylmethyl]phosphonic acid diisopropyl esters . Furthermore, it was found that P–C bonds could be easily cleaved in the gas phase under our experimental conditions.…”