Reactions of 4a-Peroxides and 4a-Pseudobases of N10- and N5-Phenethylflavins

Article abstract of DOI:10.1021/ja00535a035

A number of N⁵,N¹⁰-dialkylisoalloxazines have been synthesized in which either the N⁵ or the N¹⁰ substituent is a meta-substituted phenethyl group.Some of these compounds have been subjected to experiments in order to determine whether an intramolecular transfer of oxygen can occur between the flavin and the phenethyl group (a model of monooxygenase).When in the 1,5-dihydro reduced state, N⁵-alkyl-substituted isoalloxazines react with molecular oxygen to dive 4a-hydroperoxy derivatives.The hydroperoxides of the N⁵-ethyl-N¹⁰-phenethylflavins provide 4a-pseudobases on spontaneous decomposition.These in turn undergo ring contraction in base to yield 10a-spirohydantoins (Scheme V).The structure of 10a-spirohydantoin (28b) is as established by X-ray crystallographic technique.Spontaneous decomposition of 4a-hydroperoxides is not accompanied by intramolecular oxygen transfer to the phenethyl substituent groups at N¹⁰ or N⁵ (eq.4) 10a-Spirohydantoins may also be obtained by base treatment of 4a-pseudobases that have been prepared separately from the oxidized isoalloxazine (i.e., flavinium cation). 4a-(Allylperoxy)flavin derivatives, obtained by addition of alkyl peroxides to flavinium cations, undergo both spontaneous and photochemocal conversion to 10a-spirohydantoin.These findings are discissed in therms of proposals which have been made for the mechanism of action of flavoenzyme monooxygenases.