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Absolute Stereochemistry of a 4 a‐Hydroxyriboflavin Analogue of the Key Intermediate of the FAD‐Monooxygenase Cycle
Author(s) -
Iwahana Soichiro,
Iida Hiroki,
Yashima Eiji,
Pescitelli Gennaro,
Di Bari Lorenzo,
Petrovic Ana G.,
Berova Nina
Publication year - 2014
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201304393
Subject(s) - chemistry , chirality (physics) , flavin group , stereochemistry , diastereomer , circular dichroism , absolute configuration , time dependent density functional theory , enantioselective synthesis , adduct , monooxygenase , density functional theory , enzyme , computational chemistry , catalysis , organic chemistry , cytochrome p450 , physics , chiral symmetry breaking , quantum mechanics , nambu–jona lasinio model , quark
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.