Synthesis of bridged dinucleosides

Article abstract of DOI:10.1016/S0040-4020(01)89771-4

A series of di-(adenosin-N⁶-yl) alkanes (1b) - (11) has been prepared by reaction of the appropriate diaminoalkanes with 6-chloro-9-β-D-(2,3,5-tri-O-acetyl)-ribofuranosyl-purine (2) followed by ammonolysis. Alternatively, an analogous reaction with 6-chloro-9-β-D-(2,3-O-isopropylidene)-ribofuranosylpurine (3) produced an intermediate which could be phosphorylated at the 5′-position prior to hydrolytic removal of the isopropylidene group. 4-(1,2,4-Triazolo)-1-(β-D-2,3,5-tri-O-acetyl ribofuranosyl)-2(1H)-pyrimidone (7) was an effective intermediate for the preparation of di-(cytidin-N⁴-yl) alkanes (8a), (8b), and (8c) from the appropriate diaminoalkanes. The longer chain di-(adenosin-N⁶-yl) alkanes are very effective inhibitors of adenosine kinase. In addition an approach to the di-(adenosin-N⁶-yl) alkanes is described which should allow tritium labelling of the alkyl chain.