1,N6-Etheno-Bridged Adenines and Adenosines. Alkyl Substitution, Fluorescence Properties, and Synthetic Applications

Article abstract of DOI:10.1021/ja00522a055

It has been shown that the reaction of chloroacetaldehyde with adenosine at pH 4.5 and 37 deg C that produces the fluorescent ε-adenosine species will not develop interfering fluorescence with N⁶-alkyladenosines.The preferred site of methylation and benzylation of ε-adenosine and ε-adenine was established as N(9) (a) by acidic ring opening of the products to substituted aminobiimidazoles in which the two etheno protons were nonequivalent; (b) by reaction of N⁶-substituted adenines with chloroacetaldehyde followed by polyphosphoric acid to dehydrate the intermediate to an N(9)-substituted ε-adenine for an unequivocal synthesis.The fluorescence of the ε-adenosine and ε-adenine species at pH 7.0 has again been confirmed, and the fluorescence properties of their N(9)-alkylated derivatives under neutral and acidic conditions have been determined.It has been shown possible, earlier reports to the contrary, to prepare N⁶-substituted adenosines through Schiff-base formation on the 6-NH2.The general method involves the use of sodium cyanohydridoborate to bring about reductive amination of aldehydes and ketones at acidic pH and is exemplified by the synthesis of N⁶-ethyladenosine, N⁶-benzyladenosine, and N⁶-furfuryladenosine (kinetin riboside), using large excesses of aldehyde and reducing agent.