Total synthesis of certain 2-, 6-mono- and 2,6-disubstituted-tubercidin derivatives. Synthesis of tubercidin via the sodium salt glycosylation procedure.
Direct glycosylation of the sodium salt of 4,6-dichloro- or 4,6-dibromo-2-methylthiopyrrolo[2,3-d]pyrimidine with 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide gave good yield of the corresponding N7-glycosylated pyrrolo [2,3-d]pyrimidine. The intermediate 4-amino-6-chloro-2-methylthio-7-beta-D-ribofuranosylpyrrolo[2,3-d] pyrimidine provided a new synthetic route to tubercidin, via 6-chlorotubercidin. 6-Chloro-2-methoxytubercidin was also obtained from 10 via the methylsulfone. Application of this glycosylation procedure to 4,6-dichloro- or 4,6-dibromo-2-methylpyrrolo [2,3-d]-pyrimidine also furnished the corresponding N7-glycosyl derivatives with beta-configuration. Dehalogenation of gave 2-methyl-tubercidin and bromination with bromine in a buffered solution gave 5,6-dihalo-2-methyltubercidin. Several new 2,6-disubstituted tubercidin derivatives were prepared from these glycosyl intermediates. This new sodium salt glycosylation procedure was found to be superior to other procedures for the total synthesis of these halogenated 7-deazapurine nucleosides.
D055598:Chemical Phenomena; D002621:Chemistry; D006027:Glycosides; D009682:Magnetic Resonance Spectroscopy; D012263:Ribonucleosides / Q000138:chemical synthesis*; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014372:Tubercidin / Q000031:analogs & derivatives / Q000138:chemical synthesis*
D006027:Glycosides; D012263:Ribonucleosides; D014372:Tubercidin