Advances in Green Catalysis for the Synthesis of Medicinally Relevant N-Heterocycles

Abstract

N-heterocycles, both saturated and unsaturated, are ubiquitous biologically active molecules that are extremely appealing scaffolds in drug discovery programs. Although classical synthetic methods have been developed to access many relevant N-heterocyclic scaffolds, representing well-established and reliable routes, some do not meet the needs of sustainability. In this context, several advances have been made towards the sustainable synthesis of N-heterocycles. This review focuses on the most recent examples from the last five years of catalytic synthesis of several heterocyclic compounds of medicinal relevance. Thus, the synthesis of isoindoloquinazolines, quinazolines and azaindoles, among others, are covered. The synthetic methods selected include the use of homogeneous and heterogeneous catalysts and the use of alternative and sustainable methods such as, for example, metal-catalyzed acceptorless coupling and one-pot reactions. The green aspects of the individual synthetic approaches are highlighted, and the scope of each methodology is described.

Recent Advances in the Green Synthesis of Active N-Heterocycles and Their Biological Activities

“…N -heterocyclic compounds have become progressively in demand for their exclusive structural identity exhibiting myriad medicinal and pharmaceutical activities [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. The saturated and unsaturated N -heterocyclic analogues have exceptionally interesting architecture for drug design and development [ 7 , 17 , 18 , 19 , 20 , 21 ]. Numerous naturally occurring N -heterocyclic scaffolds are the major components of several pharmaceuticals, antibiotics, nucleic acids, etc., which unveil their importance and compulsion in drug discovery [ 22 , 23 ].…”

“…However, the synthetic methods focusing on the greener version are comparatively fewer, leaving ample scope for exploring this area of research [ 43 ]. Among them, the environmentally benign procedures leading to convenient access to biologically active complex N -heterocyclic frameworks with medicinal and pharmaceutical significance are rarer [ 19 , 44 ]. The pharmaceutical, agrochemical, and many other industries are regularly generating tremendous hazardous and toxic wastes, elevating environmental burden significantly.…”

The Immobilization of Laccase on Mixed Polymeric Microspheres for Methyl Red Decomposition

“…Plenty of substances are required to meet the growing demands of the expanding markets such as health, pharmaceutical, and fine chemical companies [1,2]. Catalysts are used to respond quickly to the demand for such materials and to accelerate growth in the chemical industry [3,4]. Scientists are increasingly concerned about environmental issues, and they are investigating sustainable alternatives to conventional catalysts, including the use of enzymes [5].…”

Bimetallic Catalyzed Synthesis of 2-Arylindoles

“…N-Heterocyclic scaffolds are crucial in synthetic and medicinal chemistry. 1,2 The synthesis of indole-derivatives has attracted enormous interest due to their pharmacological properties as anticancer, antioxidant, and anti-inflammatory drugs (Figure 1). 3…”