Synthesis and photophysical properties of 5-(3′′-alkyl/aryl-amino-1′′-azaindolizin-2′′-yl)-2′-deoxyuridines

Abstract

The Groebke–Blackburn–Bienayame (GBB) reaction has been used for the efficient synthesis of novel fluorescent 5-azaindolizino-2′-deoxyuridines starting from commercially available thymidine following two strategies. Thus, thymidine was converted to diacetylthymidine, which on potassium persulphate oxidation afforded 3′,5′-di-O-acetyl-5-formyl-2′-deoxyuridine. In strategy A, diacetylated 5-formyldeoxyuridine was reacted with a variety of 2-aminopyridines and alkyl/aryl isocyanides under optimized GBB reaction conditions followed by deacetylation of the resulting GBB products to afford 5-azaindolizino-2′-deoxyuridines in 83 to 95% overall yields. In strategy B, diacetylated 5-formyldeoxyuridine was first deacetylated, which on GBB reaction under standardised conditions with 2-aminopyridines and alkyl/aryl isocyanides afforded the desired 5-azaindolizino-2′-deoxyuridines in 21 to 23% overall yields, which clearly indicates that strategy A is far more efficient than strategy B. The emission spectra of the synthesized 5-azaindolizino-2′-deoxyuridines exhibited a strong band around 360 nm (excitation at 239 nm) in fluorescence studies. Photophysical studies of these nucleosides showed a high level of fluorescence with Stokes shift in the range 59–126 nm, which indicated their potential for the study of the local structure and dynamics of nucleic acids involving them.