SYNTHESIS OF 3',5'-DITHIOTHYMIDINE AND RELATED-COMPOUNDS

When 3',5'-di-O-mesylthymidine 7 is heated first with triethylamine in ethanol solution and then with the sodium salt of 4-methoxyphenylmeth anethiol 9 in N,N-dimethylacetamide (DMA) solution, the bis(sulfide) 1 1a is obtained in high yield; when the dimesyl ester 9 is treated with the same thiolate salt in hexamethylphosphoric triamide (HMPA) soluti on at room temperature, the threo-bis(sulfide) 12a is obtained stereos pecifically. Treatment of the two bis(sulfides) 11a and 12a first with 2-nitrobenzenesulfenyl chloride 10 in acetic acid-dichloromethane (1: 9v/v) at 0 degrees C and then with zinc in hot acetic acid gives 3',5' -dithiothymidine 5a and the cyclic disulfide 16, respectively, as crys talline solids in good overall yields, Although attempts to isolate th e pure threo-dithio compound 12b lead to the formation of the cyclic d isulfide 16, when the crude material is treated with 2,2-dimethoxyprop ane in the presence of acid, its 3',5'-S-isopropylidene derivative 17 is obtained and isolated as a crystalline solid in good overall yield.