DEFINED DIMENSIONAL ALTERATIONS IN ENZYME SUBSTRATES. SYNTHESIS AND ENZYMATIC EVALUATION OF SOME LIN-NAPHTHOPURINES.

摘要

The development of methodology for the regioselective synthesis of tetra-beta-substituted naphthalenes via a combination of bicyclo{4.2.0}octa-1,3,5-triene and aryl trimethylsilyl chemistry led to the synthesis of benzimidazo{5,6-g}-8H-quinazolin-9-one and benzimidazo{5,6-g}-6H,8H-quinazoline-7,9-dione 4.8 (ANGSTROM) laterally extended dimensional derivatives of hypoxanthine and xanthine. These compounds, lin-naphthohypoxanthine and lin-naphthoxanthine, exhibited intense fluorescence. lin-Naphthoxanthine was not oxidized to lin-naphthouric acid by xanthine oxidase but functioned as a noncompetitive inhibitor. However, lin-naphthohypoxanthine was readily converted to lin-naphthoxanthine by xanthine oxidase. In this reaction, lin-naphthohypoxanthine functioned as a competitive inhibitor of xanthine oxidase. The enzymatic results for the naphthologs when compared with the benzologs demonstrate, in part, a useful application of defined dimensional probes for determining the limiting spatial restrictions of the binding region for xanthine oxidase.;Investigation of alternative synthetic routes to the lin-naphthopurines via preformed tetra-beta-substituted naphthalenes or other benzenoid precursors reinforced the intrinsically unfavorable substitution pattern of naphthalene and reminded us of the problems associated with the formation of halomethyl groups nitrogen-substituted aromatics. In exploring the alternative synthetic routes several 4,5-disubstituted-1,2-di(halomethyl)-benzene compounds and their potential precursors were made wherein the halogen was Cl, Br, I and the disubstitution was with H, OMe, NHAc, NHCOPh, or N(Ac)(,2).