SYNTHESIS AND CHARACTERIZATION OF THE 6-DEAZA DERIVATIVE OF COENZYME PQQ, METHYL 4,5-DIHYDRO-4,5-DIOXOBENZ[G]INDOLE-2-CARBOXYLATE

The synthesis of the 6-deaza derivative of coenzyme PQQ, methyl 4,5-dihydro-4,5-dioxobenz[g]indole-2-carboxylate (4), is described, and its physical and chemical properties are compared to those of the trimethyl ester of PQQ (2) and the methyl ester of 7,9-didecarboxy PQQ (3). The synthesis of 4 was achieved by starting with 1-aminonaphthalene and constructing 2-carbomethoxybenz[g]indole (7) by a Japp-Klingemann reaction with methyl alpha-methylacetoacetate and a subsequent Fischer indolization reaction. The quinone function was introduced by a Fremy's salt oxidation of 5-aminoindole 9 which was prepared from 7 by regioselective nitration and catalytic hydrogenation. From the physical properties, it can be recognized that the peri pyridine nitrogen and the ester groups at the 7- and 9-positions considerably affect the electronic nature of the molecules. This is reflected on the reactivities of the quinones in the acetone-adduct formation, the reaction with phenylhydrazine, and the aerobic autorecycling oxidation of benzylamine. The significant roles of the pyridine nitrogen and the ester groups in these reactions are discussed.