Laccases: Versatile Biocatalysts for the Synthesis of Heterocyclic Cores.

Ana Catarina Sousa,Lígia O Martins,M Paula Robalo

doi:10.3390/molecules26123719

Abstract

Laccases are multicopper oxidases that have shown a great potential in various biotechnological and green chemistry processes mainly due to their high relative non-specific oxidation of phenols, arylamines and some inorganic metals, and their high redox potentials that can span from 500 to 800 mV vs. SHE. Other advantages of laccases include the use of readily available oxygen as a second substrate, the formation of water as a side-product and no requirement for cofactors. Importantly, addition of low-molecular-weight redox mediators that act as electron shuttles, promoting the oxidation of complex bulky substrates and/or of higher redox potential than the enzymes themselves, can further expand their substrate scope, in the so-called laccase-mediated systems (LMS). Laccase bioprocesses can be designed for efficiency at both acidic and basic conditions since it is known that fungal and bacterial laccases exhibit distinct optimal pH values for the similar phenolic and aromatic amines. This review covers studies on the synthesis of five- and six-membered ring heterocyclic cores, such as benzimidazoles, benzofurans, benzothiazoles, quinazoline and quinazolinone, phenazine, phenoxazine, phenoxazinone and phenothiazine derivatives. The enzymes used and the reaction protocols are briefly outlined, and the mechanistic pathways described.

Highlights

Heterocyclic compounds are important molecules among the applied branches of organic chemistry. They are abundant in natural products and their properties are useful in the design of several pharmaceuticals and new materials. They are key structural components in many molecular drugs, due to their ability to hydrogen bond and other properties, exhibiting an overall inhibitor effect retarding the progression of several diseases [1,2,3]
Organic synthesis of chemicals suffers from several drawbacks, including the high cost of chemicals, cumbersome multi-step reactions and toxicity of reagents
Most reported methods in the literature involve the use of excess amounts of expensive and toxic oxidants at abrasive reaction conditions and environmentally unfriendly solvents [8,9,10]

Summary

Introduction

Heterocyclic compounds are important molecules among the applied branches of organic chemistry They are abundant in natural products and their properties are useful in the design of several pharmaceuticals and new materials. Laccases couple the oxidation of a wide range of aromatic substrates with the reduction of molecular oxygen to water They are very interesting biocatalysts that have attracted considerable attention in the last decades in environmental and biotechnological processes, including drug, food, textile, cosmetics, and biodegradation of organic compounds in wastewater, enzymatic biofuel cells, among others [14,15,16,17,18,19]. Laccase reactions, which promote aromatic compounds oxidation in the presence of oxygen as a co-substrate, do not use toxic reagents and do not display hazardous side effects, have received increasing attention in the synthesis of fine chemicals.

Bacterial Versus Fungal Laccases

Synthesis of Five-Membered Ring Heterocycles

Synthesis of 2-Arylbenzimidazoles

Synthesis of Phenazine Derivatives