Pyrrolopyrimidine nucleosides. IV. The synthesis of certain 4,5‐disubstituted‐7‐(β‐d‐ribofuranosyl)pyrrolo[2,3‐d]pyrimidines related to the pyrrolo[2,3‐d]pyrimidine nucleoside antibiotics

The treatment of 4‐chloro‐7‐(2′,3′,5′‐tri‐O‐acetyl‐β‐D‐ribofuranosyl)pyrrolo[2,3‐d]pyrimidine (4) with N‐bromoacetamide in methylene chloride has furnished the 5‐bromo derivative of 4 which on subsequent deacetylation provided a good yield of 5‐bromo‐4‐chloro‐7‐(β‐D‐ribo‐furanosyl)pyrrolo[2,3‐d] pyrimidine (6). Assignment of the halogen substituent to position 5 was made on the basis of pmr studies. Treatment of 6 with methanolic ammonia afforded 4‐amino‐5‐bromo‐7‐(β‐D‐ribofuranosyl)pyrrolo[2,3‐d ]pyrimidine (8, 5‐bromotubercidin) and a subsequent study has revealed that the 4‐chloro group of 6 was replaced preferentially in a series of nucleophilic displacement reactions. The analogous synthesis of 4,5‐dichloro‐7‐(β‐D‐ribo‐furanosyl)pyrrolo[2,3‐d]pyrimidine (13b) and 4‐chloro‐5‐iodo‐7‐(β‐D‐ribofuranosyl)pyrrolo[2,3‐d]pyrimidine (13a) from 4 furnished 5‐chlorotubercidin (15) and 5‐iodotubercidin (14), respectively, on treatment of 13b and 13a with methanolic ammonia. The possible biochemical significance of these tubercidin derivatives is discussed.