A Sustainable Synthesis of Asymmetric Phenazines and Phenoxazinones Mediated by CotA‐Laccase

Abstract

An efficient and sustainable one-step procedure for the synthesis of new asymmetric phenazines and phenoxazinones from commercially available ortho-substituted diamines and orthosubstituted hydroxyamines is reported. In this study we have expanded the substrate scope of CotAlaccase-catalyzed aerobic oxidations through the use of aromatic amines presenting variable functional groups, including N-substitution, contributing to the rational synthesis of different heterocyclic scaffolds. The transformations proceed smoothly through a cascade of oxidative reactions to the benzoquinonediimine intermediates followed by nucleophilic addition, intramolecular cyclization and aromatization, all performed in mild conditions.

Synthesis of Azobenzene Dyes Mediated by CotA Laccase

“…The oxidation of simple modela romatic amines has been used as as imple approacht oi dentify the substrate's structural features that are important for the success of the enzyme-catalysed redoxr eactions as well as to understandt he correspondent mechanistic pathways. [32][33][34][35][36] The electronic nature of the substituents and their positions relative to the reactive amino group in the aromatic ring of the substrates showed to be decisive in the formation of products with differents tructures. Several different cores, such as dimers, trimers, phenoxazines,p henoxazinones and carbazoles were obtainedu sing CotA laccase as biocatalyst, being their formationd elimited by the balance between the substrate's ability to generateastable radical intermediate, promoted by laccase, andi ts nucleophilicity as ap artner in the sequential coupling reaction.…”

“…[32] Overall the results obtained indicate that the electronic character of the substituent groups and their relative positiont o the aminog roup determine the reaction course and the products typef ormed, supporting the resultsf ound in our previous studies. [32][33][34] The proposed structures were based in NMR and ESI-MS data analysisa nd data in the literature. [9,10,14] The 1 HNMR spectra of the products 2a-c and 3 showeds imilarp atterns,c haracterised by the presence of two doublets, shiftedd ownfield when compared with the corresponding substrates (1a-d).…”

“…[28][29][30][31] In the last years, our group have developed several eco-friendly protocols towardst he synthesis of different heteroaromatic compounds using CotA laccase from Bacillus subtilis,a sb iocatalyst in the oxidation of primary aromatic amines. [32][33][34] In these studies, azobenzene derivatives were obtained as secondary products, showingt he feasibility of CotA laccase to produce this type of compounds. This information prompted us to extend our studies for the formation of these compounds,u sing CotA laccase and the CotA laccase/ABTS systems.…”

Study on improving the stability of adsorption-encapsulation immobilized Laccase@ZIF-67

“…As a clean, effective and green biocatalyst, its theoretical research and technical application have been developed for decades. Due to their low specificity, several organic compounds such as polycyclic aromatic hydrocarbons [ 1 ], aromatic amines [ 2 ], phenolic compounds [ 3 ], etc. are the substrates of laccase [ 4 ].…”

Structure and Bioactive Properties of Novel Textile Dyes Synthesised by Fungal Laccase

“…The chemical route of phenazine synthesis requires the use of coupling agents and additives such as benzene, BBr 3 , DMF, and various other harsh, toxic, and mutagenic compounds [12]. In contrast to the chemical synthesis, phenoxazine and phenazine compounds can be easily obtained through the biocatalysis due to the action of fungal or bacterial laccase and the use of aminophenolic precursors [13][14][15][16]. Phenoxazines can be synthesised in laccase-mediated homomolecular coupling reactions of different ortho-aminophenols or ortho-aminonaphtalenes [13,14], whereas phenazines can be obtained through the heteromolecular transformation of phenol derivatives with aromatic amines [15,17].…”