Determination of the Absolute Configuration of Flexible Molecules by ab Initio ORD Calculations: A Case Study with Cytoxazones and Isocytoxazones

Ab initio calculations of the optical rotatory power of the natural cytokine modulator cytoxazone 1 and its trans-diastereomer 2, as well as the structural isomers cis-3 and trans-4 isocytoxazones, have been performed at four different wavelengths (589, 546, 435, and 405 nm) by Density Functional Theory. The calculation of ORD curves provides a reliable method for the assignment of absolute configuration of these conformationally flexible molecules. The absolute configurations of isocytoxazones has been established as (+)-(4R,5S)-cis-3 and (+)-(4S,5S)-trans-4.