130148-58-2Relevant academic research and scientific papers
Regioselective Synthesis of Imidazoquinazoline Quinone Nucleosides and Quinazoline Amino Nucleosides. Studies of Their Xanthine Oxidase and Purine Nucleoside Phosphorylase Substrate Activity
O'Hara Dempcy, Robert,Skibo, Edward B.
, p. 776 - 785 (2007/10/02)
The regioselective synthesis of 3-ribofuranosylimidazoquinazoline-4,8,9(3H,7H)-trione (1) (benzoquinone-stretched-out inosine) and 8-(ribofuranosylamino)quinazolin-4(3H)-one (2) was carried out in conjunction with the design of reductive alkylating nucleosides and new purine nucleoside mimics, respectively.The preparation of 1 was carried out by regioselective ribosylation of 4-nitroimidazoquinazolin-8(3H,7H)-one (3) followed by nitro group reduction, Fremy oxidation, and deacetylation.Regiocontrol of ribosylation has steric origins: the 4-nitro group of 3 directs silylation to the N(1) position, which results in ribosylation exclusively at the N(3) position under Vorbrueggen reaction conditions.Regiocontrol during the preparation of 2 was possible by generating a stabilized ribofuranosyl carbocation, which selectively reacts with the amine group of the base.Nucleoside 1 is a purine-like quinone by virtue of its oxidation by xanthine oxidase.The potential inosine mimic 2 does not undergo phosphorolysis by purine nucleoside phosphorylase (PNPase), but the base form (8-aminoquinazolin-4(3H)-one) does bind to the PNPase active site as tightly as hypoxanthine.Factors which contribute to this binding behavior are discussed.
