Synthesis, separation, and absolute configuration of the two 5-(2,2-dibromocyclopropyl) and four 5-(2-bromocyclopropyl) diastereomers of 2′-deoxyuridine

The reaction of 3-N-3′,5′-di-O-tribenzoyl-2′-deoxy-5-vinyluridine (2) with dibromocarbene, generated from PhHgCBr3 under thermal neutral conditions, yielded a mixture of the 5-[(1S)-2,2-dibromocyclopropyl]- (3a) and 5-[(1R)-2,2-dibromocyclopropyl]-3-N-3′,5′-di-O-tribenzoyl-2′-deoxy-5-vinyluridine (4a) diastereomers, which were separated (1:1 ratio). Treatment of 3a and 4a with methanolic ammonia afforded the respective 5-[(1S)-2,2-dibromocyclopropyl]- (3b) and 5-[(1R)-2,2-dibromocyclopropyl]-2′-deoxyuridines (4b). The absolute configuration of 3b has been established by X-ray crystal structure determination. Monodebromination of 3b, using zinc dust in HOAc at 50 °C, gave a mixture of the 5-[(1S,2S)-2-bromocyclopropyl]- (5) and 5-[(1S,2R)-2-bromocyclopropyl]- (6) diastereomers, which were separated and their respective configuration assigned by 1H nuclear magnetic resonance. A similar monodebromination of 4b yielded the 5-[(1R,2R)-2-bromocyclopropyl]- (7) and 5-[(1R,2S)-2-bromocyclopropyl]-2′-deoxyuridine (8) diastereomers. Relationships between physicochemical properties, such as melting point and tlc Rf value, and the configuration of the chiral cyclopropyl carbon(s) were observed. The chemical shifts for the 13C nuclear magnetic resonances are also of diagnostic value for determination of the respective configuration of the cyclopropyl carbons of the 5-(2-bromocyclopropyl) isomers 5–8. Keywords: bromocyclopropanes, 2′-deoxyuridines, absolute configuration, antiviral activity.