Structural characterization of a novel degradant of the antifungal agent posaconazole

A number of degradants of the antifungal agent posaconazole have been isolated and characterized. Degradation chemistry occurs primarily in the piperazine moiety located near the center of the molecule and typically involves oxidative processes. At least one ring contraction product has also been fully characterized by MS and NMR methods. We report the isolation and characterization of a novel degradant of posaconazole in which remnants of the piperazine ring have been incorporated into a 1,4-benzodiazepine moiety. The structure of the novel degradant was unequivocally established through accurate mass measurements, MS/MS studies, H/D exchange, and a range of 2D NMR experiments that included 1,1-ADEQUATE and covariance calculated HSQC-1,1-ADEQUATE spectra.