7-Substituted 7-Deaza-2′-deoxyadenosines and 8-Aza-7-deaza-2′-deoxyadenosines: Fluorescence of DNA-Base Analogues Induced by the 7-Alkynyl Side Chain

Abstract

7-Alkynylated 7-deazaadenine (pyrrolo[2,3-d]pyrimidin-4-amine) 2′-deoxyribonucleosides show strong fluorescence which is induced by the 7-alkynyl side chain (Table 3). A large Stokes shift with an emission around 400 nm is observed when the compound is irradiated at 280 nm. The solvent dependence indicates the formation of a charged transition state. The fluorescence appears when the triple bond is in conjugation with the heterocyclic base. Electron-donating substituents at the triple bond increase the fluorescence, while electron-withdrawing residues reduce it. In comparison, the 7-alkynylated 8-aza-7-deazaadenine (pyrazolo[3,4-d]pyrimidin-4-amine) 2′-deoxyribonucleosides are rather weakly fluorescent (Table 4). Quantum yields and fluorescence decay times are measured. The synthesis of the 7-alkynylated 7-deaza-2′-deoxyadenosines and 8-aza-7-deaza-2′-deoxyadenosines was performed with 7-deaza-2′-deoxy-7-iodoadenosine (6) or 8-aza-7-deaza-2′-deoxy-7-iodoadenosine (22) as starting materials and employing the Pd0-catalyzed cross-coupling reaction with the corresponding alkynes (Schemes 1, 4, and 5). Catalytic hydrogenation of the side chain of the unsaturated nucleosides 5 and 17 afforded the 7-alkyl derivatives 18 and 19, respectively, which do not show significant fluorescence (Scheme 2).