SYNTHESIS OF ISOMERIC ANALOGS OF COENZYME PYRROLOQUINOLINE QUINONE (PQQ)

Three isomeric analogues 2-4 of the redox-active coenzyme oxo-1H-pyrro lo[2,3-f]quinoline-2,7,9-tricarboxylic acid (1, PQQ, methoxatin) were synthesized from methoxynitroanilines 8, 9 and 10 a, respectively. Rea ction of the diazonium salts of each of the starting compounds with et hyl alpha-methylacetoacetate gave the corresponding substituted phenyl hydrazones of ethyl pyruvate. These intermediates underwent acid-catal yzed Fischer indolization and gave the esters 13, 17 and 25, respectiv ely. Reduction to the corresponding aminoindoles with hydrogen over Pd /C, followed by Doebner-von Miller quinoline synthesis with dimethyl t rans-2-ketoglutaconate, oxidation of the intermediate methoxy compound to the o-quinone, and hydrolysis of triester products gave 2, 3, and 4, respectively. These isomers will serve as authentic examples to def ine their possible formation in nature and will also serve as isosteri c probes to define the binding of PQQ at active sites in PQQ-requiring quinoproteins.