title: Determination of the absolute configurations of natural products via density functional theory calculations of optical rotation, electronic circular dichroism, and vibrational circular dichroism: the cytotoxic sesquiterpene natural products quadrone, suberosenone, suberosanone, and suberosenol A acetate.
abstract: The determination of the absolute configurations (ACs) of chiral molecules using the chiroptical techniques of optical rotation (OR), electronic circular dichroism (ECD), and vibrational circular dichroism (VCD) has been revolutionized by the development of density functional theory (DFT) methods for the prediction of these properties. Here, we demonstrate the significance of these advances for the stereochemical characterization of natural products. Time-dependent DFT (TDDFT) calculations of the specific rotations, [alpha](D), of four cytotoxic natural products, quadrone (1), suberosenone (2), suberosanone (3), and suberosenol A acetate (4), are used to assign their ACs. TDDFT calculations of the ECD of 1 are used to assign its AC. The VCD spectrum of 1 is reported and also used, together with DFT calculations, to assign its AC. The ACs of 1 derived from its [alpha](D), ECD, and VCD are identical and in agreement with the AC previously determined via total synthesis. The previously undetermined ACs of 2-4, derived from their [alpha](D) values, have absolute configurations of their tricyclic cores identical to that of 1. Further studies of the ACs of these molecules using ECD and, especially, VCD are recommended to establish more definitively this finding. Our studies of the OR, ECD, and VCD of quadrone are the first to utilize DFT calculations of all three properties for the determination of the AC of a chiral natural product molecule.
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, California 90089-0482, USA. pstephen@usc.edu
authors.forename: P J
authors.initials: PJ
authors.lastname: Stephens
authors.forename: D M
authors.initials: DM
authors.lastname: McCann
authors.forename: F J
authors.initials: FJ
authors.lastname: Devlin
authors.forename: A B
authors.initials: AB
authors.lastname: Smith
mesh_terms: D000818:Animals; D037421:Anthozoa / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry* / Q000494:pharmacology; D002942:Circular Dichroism; D015394:Molecular Structure; D009904:Optical Rotation; D012717:Sesquiterpenes / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D001688:Biological Products; D012717:Sesquiterpenes; C513512:suberosanone; C513513:suberosenol A acetate; C513511:suberosenone; C016711:quadrone