Determination of the absolute configuration and solution conformation of the antifungal agents ketoconazole, itraconazole, and miconazole with vibrational circular dichroism.
The absolute configuration assignments of three antifungal agents, (+)-(2R,4S)-ketoconazole, (+)-(2R,4S)-itraconazole (with (S)-configuration at the sec-butyl group) and (+)-(S)-miconazole nitrate have been confirmed by using vibrational circular dichroism (VCD). For these three antifungal drugs, this study also provides evidence for the most abundant conformations of miconazole and for the relative conformations of the azole, dichlorophenyl, and methoxyphenyl groups in ketoconazole and itraconazole, in chloroform solution.
Dunmire
David
D
Department of Chemistry, Syracuse University, Syracuse, New York 13244-4100, USA.
Freedman
Teresa B
TB
Nafie
Laurence A
LA
Aeschlimann
Christine
C
Gerber
John G
JG
Gal
Joseph
J
D000935:Antifungal Agents / Q000737:chemistry*; D002942:Circular Dichroism; D017964:Itraconazole / Q000737:chemistry*; D007654:Ketoconazole / Q000737:chemistry*; D008825:Miconazole / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism
D000935:Antifungal Agents; D012996:Solutions; D017964:Itraconazole; D008825:Miconazole; D007654:Ketoconazole