1H and 13C nuclear magnetic resonance studies of the sites of protonation in itraconazole and fluconazole.
1H and 13C nuclear magnetic resonance spectra of itraconazole were measured in neutral solution, and upon addition of varying amounts of deuterated hydrochloride acid. The comparison of the chemical shift in the different solutions revealed the high proton affinity of the piperazine nitrogen N26. Upon addition of a surplus of acid, the triazole ring was protonated. Corresponding observations were made for fluconazole.
Inkmann
E
E
Pharmaceutical Institute, University of Würzburg, Germany.
Holzgrabe
U
U
D000935:Antifungal Agents / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry; D015725:Fluconazole / Q000737:chemistry*; D017964:Itraconazole / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011522:Protons; D012996:Solutions
D000935:Antifungal Agents; D011522:Protons; D012996:Solutions; D017964:Itraconazole; D002244:Carbon; D015725:Fluconazole