PHOTOCHEMISTRY OF DI(DEOXYRIBONUCLEOSIDE) METHYLPHOSPHONATES CONTAINING N-3-METHYL-4-THIOTHYMINE

(Rp)- and (Sp)-5'-N-3-methyl-4-thiothymidine 3'-(thymidinyl methylphosphonate) (Tpm(3)s(4)T) (11a and 11b), respectively, have been synthesized in order to elucidate their photochemical behavior in comparison with that of their phosphate congener 1b. The dinucleoside methylphosphonates proved to be less rapidly photolyzed than 1b and gave more photoproducts. The structure and stereochemistry of each photoproduct were determined by NMR studies. A plausible mechanism to explain the formation of the major photoproducts has been proposed. It involves two pathways: either cycloaddition or radical coupling. The former one led to thietane derivatives, the formation of which is of relevance to the mechanism to give (6-4) bipyrimidine photoproducts in DNA. Most of the other photoproducts were probably formed from a biradical generated via hydrogen abstraction from the C5 methyl of the Tp-part of each dimer. Compounds 15 which represent a new type of photoproduct in the nucleic acid series are most likely formed by this route. Another significant finding of this study was that the Rp dinucleoside methylphosphonate (11a) is a better mimic of the phosphate backbone, as found in DNA, than its Sp diastereomers (11b).