Evaluation of the Quantitative Contribution of a Phenyl Group on C(2) of 8-Azaadenosine to the Binding with Adenosine Deaminase: a New Synthesis of 8-Azaadenosine. XI.

The introduction of a phenyl group on C(2) of 8-azaadenosine increases binding to the adenosine deaminase enzyme (ADA). This stability increment has been quantitatively evaluated in both 8-azaadenosines and 9-(2',3'-dihYdroxypropyl)-8-azaadenines; it resulted nearly equivalent in the two series. 8-Azaadenosine has been synthesized through a new route employing fully protected beta-D-ribofuranosyl-1-azide. Instead, the stability difference in 9-(n-alkyl)-8-azaadenines, owing to the inactivity of the C(2) unsubstituted compounds, could not be evaluated. Consideration of the enantioselectivity of the ADA enzyme toward chiral 9-(2,3'-dihydroxypropyl)-8-azaadenines and 9-(2,3'-dihydroxypropyl)-8-azahypoxanthines allowed the exclusion of an appreciable structural modification in the enzyme-inhibitor complex when hydrogen on C(2) is substituted by an aryl group.