Density Functional Theory Calculations of the Optical Rotation and Electronic Circular Dichroism: The Absolute Configuration of the Highly Flexible trans-Isocytoxazone Revised

• Published in: Journal of organic chemistry Vol. 74; no. 21; pp. 8051 - 8063
• Main Authors: Kwit, Marcin, Rozwadowska, Maria D, Gawroński, Jacek, Grajewska, Agnieszka
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 06.11.2009; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Circular Dichroism - methods; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Conformation; Organic chemistry; Oxazoles - chemistry; Physical Sciences; Preparations and properties; Science & Technology; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Ultraviolet; NATURAL-PRODUCTS; AMINO-ACIDS; CHIROPTICAL PROPERTIES; ROTATORY DISPERSION; CIS-DIHYDRODIOL METABOLITES; SPECTRA; HARTREE-FOCK; COUPLED-CLUSTER CALCULATIONS; AB-INITIO CALCULATION; CHIRAL MOLECULES; Solvent effect; Molecular flexibility; Ab initio method; Prediction; Theoretical study; Circular dichroism; Solvation; Analog; Absolute configuration; Density functional method; Optical rotation; Diastereomer; Conformation; Oxygen nitrogen heterocycle
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo901175s

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.