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, H-1 and C-13 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 (1, 2) and a 3S,4R,5R,6S) and a 3R,4S,5S,6R configuration for the cis-syn cycloadducts (3, 4). In addition, conformational features of the four photocycloadducts were obtained from consideration of various H-1 NMR measurements including NOE data.