Characterization of the cis-syn and cis-anti diastereoisomers of 5-methoxypsoralen pyrone-side monocycloadducts to thymidine

The photoreaction of 5-methoxypsoralen (5-MOP) with thymidine as a DNA model compound was investigated under dry-state conditions. In this respect, a thin film of thymidine and 5-MOP in a ratio 10:1 was exposed to 350-nm UV light. Four [2 + 2] photocycloadducts were isolated in a 0.5-2.2% yield with respect to 5-MOP by HPLC and characterized as two pairs of cis-syn and cis-anti diastereoisomers, respectively, on the basis of extensive spectroscopic measurements, including UV, fast atom bombardment mass spectrometry, 1H and 13C NMR, and CD. Information concerning the absolute configuration of the four photocycloadducts was inferred from detailed nuclear Overhauser enhancement experiments. This is indicative of a 3R,4S,5R,6S and a 3S,4R,5S,6R configuration for the cis-anti cycloadducts and a 3S,4R,5R,6S) and a 3R,4S,5S,6R configuration for the cis-syn cycloadducts. In addition, conformational features of the four photocycloadducts were obtained from consideration of various 1H NMR measurements including NOE data.