title: Absolute stereochemistry of a 4 a-hydroxyriboflavin analogue of the key intermediate of the FAD-monooxygenase cycle.
abstract: The biological action of flavoenzymes, such as flavin adenine dinucleotide (FAD)-containing monooxygenase, involves the formation of oxygenated flavin derivatives, such as 4 a-hydroperoxyflavin and 4 a-hydroxyflavin, in which a new center of chirality is created at the 4 a position during the enzymatic reactions. So far, the absolute configuration of this center of chirality in natural 4 a-oxygenated flavins has remained unknown in spite of its key importance for the diverse functions of flavoenzymes. Herein, we report the 4 a-hydroxy adduct 3 of 3-benzyl-5-ethyl-10-(tetraacetyl-D-ribityl)flavinium (1), one of the key intermediates involved in the enantioselective organocatalytic oxidation of sulfides to sulfoxides. The 4 a-hydroxyflavin diastereomers (+)-3 and (-)-3, separated by HPLC, were characterized by electronic circular dichroism (CD) spectroscopy. Their absolute configurations at the 4 a position were, for the first time, determined by comparing experimental CD spectra with those calculated by means of time-dependent density functional theory (TDDFT) on DFT-optimized structures obtained after an extensive conformation analysis.
authors.affiliation: Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University, Nagoya 464-8603 (Japan).
authors.forename: Soichiro
authors.initials: S
authors.lastname: Iwahana
authors.forename: Hiroki
authors.initials: H
authors.lastname: Iida
authors.forename: Eiji
authors.initials: E
authors.lastname: Yashima
authors.forename: Gennaro
authors.initials: G
authors.lastname: Pescitelli
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Di Bari
authors.forename: Ana G
authors.initials: AG
authors.lastname: Petrovic
authors.forename: Nina
authors.initials: N
authors.lastname: Berova
mesh_terms: D002942:Circular Dichroism; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000378:metabolism*; D012256:Riboflavin / Q000031:analogs & derivatives / Q000378:metabolism*; D013237:Stereoisomerism; D013440:Sulfides / Q000737:chemistry / Q000378:metabolism; D013454:Sulfoxides / Q000737:chemistry / Q000378:metabolism
chemical_list: D013440:Sulfides; D013454:Sulfoxides; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D012256:Riboflavin
keywords: circular dichroism; conformation analysis; hydrogen bonds; solvent effects; structure elucidation