Defined Dimensional Alterations in Enzyme Substrates. lin-Naphthoadenine and lin-Naphthoadenosine

Article abstract of DOI:10.1021/jo00186a016

lin-Naphthoadenine (lin = linear) and lin-naphthoadenosine have been synthesized for the first time, on the basis of the availability of the intermediate lin-naphthohypoxanthine from a shortened, efficient synthesis. 5,6-Dimethylbenzimidazole, protected by a bulky group on N, was subjected to selective benzylic bromination.The tetrabromo product, when treated with sodium iodide under Finkelstein conditions, generated a dibromo-o-xylylene intermediate that could be trapped by maleic anhydride or N-hydroxymaleimide, with aromatization by loss of 2 HBr.This Diels-Alder cycloaddition approach to the otherwise difficult available tetra-β-substituted naphthalenes was followed by stepwise conversions of the terminal anhydride or N-hydroxyimide ring to a suitable substituted pyrimidine ring. lin-Naphthoadenine and lin-naphthoadenosine are brillantly fluorescent, exhibiting high fluorescent yields (Φ = 0.57, 0.64) and long lifetimes (τ = 20.5, 22.4 ns in ethanol purged of oxygen).Neither is a substrate for adenosine deaminase, showing that a lateral extension of 4.8 Angstroem is too great for a satisfactory fit at the enzyme active site, whereas a 2.4-Angstroem extension (lin-benzoadenine and lin-benzoadenosine) is tolerated.