SET photochemistry of flavin-cyclopropylamine systems. Models for proposed monoamine oxidase inhibition mechanisms

Article abstract of DOI:10.1021/ja00024a034

Single electron transfer (SET) induced photochemical reactions of 3-methyllumiflavin (3-MLF) with the cyclopropylamines, trans-2-phenylcyclopropylamine (1) and 1-phenylcyclopropylamine (4), have been explored with the aim of defining the nature of and mechanisms for the reaction pathways followed. The excited-state SET processes probed in this investigation were designed to model those proposed previously for inactivation of the flavine-containing enzyme, monoamine oxidase, by these same cyclopropylamines. Irradiation of 3-MLF in an N₂-purged solution containing cyclopropylamine 4 leads to generation of the C-4a,N-5-propanodihydrofiavin 14 as the major primary photoproduct. This substance, which is formed by an SET-promoted radical coupling mechanism, is transformed to the C-4a-(benzoylethyl)dihydroflavin 6 under hydrolytic conditions. Several other minor, cyclopropylamine-derived products are also generated in this reaction, again via radical pathways. In contrast, irradiation of an air-saturated solution of 3-MLF and 4 produces the epoxy ketone 8 efficiently. In this reaction, 3-MLF serves as an SET photosensitizer for the oxidative ring-opening reaction that converts 4 to 8. Finally, the C-4a,N-5-propanodihydroflavin adducts 17 and 18 are generated along with substances arising by secondary reaction of a primary product, cinnamaldehyde (20), when 3-MLF is irradiated in an N₂-purged solution containing the cyclopropylamine 1. Mechanistic aspects of these bona fide SET flavin-cyclopropylamine reactions and their possible relationship to proposals made earlier about the nature of and mechanisms for monoamine oxidase inactivation by the same cyclopropylamines are discussed.