title: Density functional theory calculations of the optical rotation and electronic circular dichroism: the absolute configuration of the highly flexible trans-isocytoxazone revised.
abstract: Ab initio calculations of the optical rotation (OR) and electronic circular dichroism (ECD) for a series of trans-diastereomers of the natural cytokine modulator cytoxazone 1-4 have been performed by density functional theory (DFT). The calculation of OR and ECD curves provides, after critical assessment, a reliable method for the assignment of absolute configuration of these conformationally flexible molecules. The effects of the level of theory used for calculations, changes of conformer equilibrium, and the solvent influence on the geometry and values of calculated OR data are discussed, leading to the conclusion that the most frequently used B3LYP/6-31G(d) method is not adequate for prediction of the absolute configuration of this type of highly flexible molecules. The absolute configurations of levorotatory trans-isocytoxazone 2 and analogues 1, 3, and 4 have been established as (-)-(4S,5S)-trans-1-4; i.e., it is in opposition to the previously published configuration (-)-(4R,5R)-trans-2.
authors.affiliation: Department of Chemistry, Adam Mickiewicz University, 60-780 Poznań, Poland. marcin.kwit@amu.edu.pl
authors.forename: Marcin
authors.initials: M
authors.lastname: Kwit
authors.forename: Maria D
authors.initials: MD
authors.lastname: Rozwadowska
authors.forename: Jacek
authors.initials: J
authors.lastname: Gawroński
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Grajewska
mesh_terms: D002942:Circular Dichroism / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D010080:Oxazoles / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet
chemical_list: D010080:Oxazoles; C117832:cytoxazone