Photoreaction of 8-methoxypsoralen with thymine and thymidine

Abstract

The photoreaction of 8-methoxypsoralen (8-MOP) with thymine and thymidine was carried out in dioxane-water frozen state and methanol solid film state respectively as a model reaction in order to elucidate the molecular basis of skin-photosensitization of furocoumarins. One major and two minor monoaddition products between 8-MOP and thymine were isolated by various chromatographic methods. Major monoadduct was characterized by various physical methods to be a $C_4$-cycloaddition product formed between 5,6-double bond of thymine and 3,4-double bond of 8-MOP with cisanti stereochemistry. Two minor adducts were proved to be stereoisomers of 3,4-adducts with unknown stereochemistry. In case of the photoreaction between 8-MOP and thymidine, two 4``,5``-monoadducts containing a pair of diatereomers each and three 3,4-monoadducts were formed. Among them, two 4``,5``-monoadducts and one 3,4-monoadduct were characterized to be $C_4$-cycloaddition products with cis-syn, trans-syn and cis-anti configuration respectively. Other than these monoadducts, 3,4,4``,5``-biadducts were formed during the photoreaction, but the isolation of each isomer of these biadducts was difficult because of its complexity and unstability. However, the formation of these biadducts was proved by UV, IR, TLC and photosplitting experiments. Tetramethylethylene (TME) quenches the fluorescence of 4``,5``-mono-adducts with relatively low efficiency(with kq. $\tau$=0.385), but reacts with 4``,5``-monoadducts effectively to form thymidine-8-MOP-TME biadducts on irradiation. These biadducts were isolated and characterized by physical methods. These observations along with the benzophenone sensitized photoaddition of 8-MOP to TME suggest the triplet mechanism for the photocycloaddition reaction of 4``,5``-monoadducts to TME.