Synthesis and characterization of dimethyl 9,10-dihydro-9,10-dioxobenzo[f]quinoline-2,4-dicarboxylate. Effect of the pyrrole nucleus on the reactivity of coenzyme PQQ

Abstract

Dimethyl 9,10-dihydro-9,10-dioxobenzo[/]quinoline-2,4-dicarboxylate (4) was synthesized, and its physical and chemical properties were compared to those of the trimethyl ester of PQQ (PQQTME,2) and the 1-methyl derivative (3). The synthesis of 4 was accomplished by a Doebner-von Miller-type annulation between 3-amino-2-naphthol and dimethyl 2-oxoglutaconate and a subsequent oxidation with Fremy's salt. The electronic effect of the pyrrole nucleus of coenzyme PQQ (1) was examined by comparing the reactivity of 4 to that of 2 and 3 in the acetone adduct formation reaction, the redox reaction with phenylhydrazine, and the aerobic autorecycling oxidation of benzylamine. The significant role of the pyrrole nucleus in conducting the intramolecular general base catalysis in the amine oxidation is discussed.

A New One-Pot Synthesis of Quinoline-2-carboxylates under Heterogeneous Conditions

“…In particular, quinoline-2-carboxylates play a predominant role as precursor of biologically active molecules [4,5,6,7,8] and as useful ligands in metal-catalyzed reactions [9,10]. Due to their importance, over the years, a variety of synthetic methodologies have been reported in the literature, which can be classified (Scheme 1) in: (i) oxidative processes, starting from the corresponding 2-methyl or 2-carbonyl quinolines [11,12]; (ii) hydrolytic reactions of cyano precursors [13]; (iii) metal-catalyzed cyclization, starting from N -aryl glycine derivatives or iminoethyl glyoxylates [14,15]; (iv) one-pot reduction-cyclization processes of 2-acylnitroarenes with α-oxoesters [16]; (v) carboxylation reactions of 2-chloro quinoline derivatives [17]; and (vi) the historical Doebner-Von Miller protocol [18].…”

“…Nevertheless, several of the reported procedures present some limitations such as restricted applicability (only few examples were reported) [11,12,13,18], low overall yields [16] and harsh reaction conditions [17]. Hence, new simple and general protocols for synthesizing these derivatives would surely be welcome.…”

Metal-free one-pot synthesis of quinoline-2,4-carboxylates via a molecular iodine-catalyzed three-component reaction of arylamines, ethyl glyoxylate, and α-ketoesters

“…As a consequence of their unique chemical and biological properties, quinoline-2-carboxylates have been increasingly pursued. Generally, quinoline 2,4-dicarboxylates were prepared from a condensation reaction of dimethyl ketoglutaconate (DKG) with substituted anilines [15][16][17][18][19][20][21] or a selective conjugate reaction of the preformed N-arylphosphazenes with α,β-unsaturated carbonyl compounds [22]. Nevertheless, these methods usually suffer from some drawbacks, such as low yield, a large amount of acid promoters needed, hardly available reactants, and the generation of stoichiometric amounts of wastes.…”

Protein Tyrosine Phosphatase 1B Inhibitors: Catechols.

“…Then 1,2-naphthoquinone 15a from the earlier work 5 was reduced to 1,2-dihydroxynaphthalene 17 using phenyl hydrazine. 7 As the catechol derivatives were easily oxidized back to naphthoquinone derivatives by atmospheric oxygen and metabolic instability was also expected, the acetylated derivatives 16 were prepared in one pot using zinc, sodium acetate, and acetic anhydride 8 to implement the pro-drug character with stability. As expected from modest activities of catechols 7 and 11, diacetoxynaphthalene 16a showed low in vitro inhibitory activity.…”