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

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