Abstract: Over the last two decades, quinoline has emerged as a privileged N-heterocycle with a wide scope of pharmacological properties. It has become an attractive moiety for drug design owing to its fascinating structure and reactivity. Accordingly, various methods have been developed for its synthesis and derivatization. Most known conventional synthesis approaches are operationally complex, require harsh reaction conditions, and tedious workup. They are time- and energy-consuming, low-yielding, and produce a significant amount of side products. In recent years, efforts have been made to reduce reaction times and develop greener routes with higher yields. This review highlights some notable developments for microwave (MW)-assisted synthesis of quinolines. It will cover key examples of MW-assisted one-pot synthesis, multicomponent reactions (MCRs), nanocatalyzed reactions in aqueous media, and other green solvents.
Introduction/Objective: The growing demand for environmentally responsible and resource-efficient processing has accelerated interest in green extraction technologies. This study aimed to develop and optimize a sustainable microwave-assisted extraction (MAE) method using natural deep eutectic solvents (NaDES) for the efficient recovery of antioxidant and enzymeinhibitory phytochemicals from twigs of Otostegia limbata, a medicinal plant of notable ethnopharmacological importance. Methods: A choline chloride–urea-based aqueous NaDES was employed as the extraction solvent. Key MAE parameters, including microwave power, solid–solvent ratio, extraction time, and NaDES concentration, were optimized using response surface methodology (RSM). Total phenolic content (TPC), total flavonoid content (TFC), DPPH radical scavenging activity (RSA), ironchelating activity (ICA), and α-amylase inhibitory activity (AIA) were used as response variables. Artificial neural network (ANN) modeling was applied to evaluate nonlinear relationships, and GC–MS analysis was conducted for phytochemical profiling. Results: Optimal extraction conditions were identified as 770 W microwave power, 30 mL/g solid–solvent ratio, 60-second extraction time, and 30% aqueous NaDES. Under these conditions, TPC (11.44 mg GAE/g DW), TFC (3.93 mg RE/g DW), RSA (2.23 mg AAE/g DW), ICA (52.69 mg EDTAE/g DW), and AIA (53.18%) were achieved. The experimental results closely matched the predicted values, confirming the model's reliability. ANN demonstrated slightly superior predictive accuracy compared to RSM. GC–MS analysis revealed key bioactive compounds, including hardwickiic acid, hardwickiic acid methyl ester, camphor, and thymol. Discussion: The combined MAE–NaDES system effectively enhanced extraction efficiency while reducing solvent toxicity and processing time. The improved predictive performance of ANN highlights its usefulness in modeling complex extraction systems. Conclusion: This study demonstrates that MAE coupled with NaDES is a rapid, efficient, and green extraction strategy for O. limbata, supporting its sustainable utilization in food, nutraceutical, and bioactive ingredient applications.
The introduction of microwave irradiation in organic synthesis has revolutionized traditional synthetic chemistry by enhancing efficiency, reducing reaction times, lowering costs, improving selectivity, increasing safety, and promoting sustainability. Consequently, microwave technology has become indispensable in diverse fields, including the synthesis of peptides, biologically active heterocycles, industrially valuable organic compounds, polymers, and materials science. The use of microwave heating has significantly advanced the synthesis of biologically relevant organic sulfides/thioethers and disulfides compared to conventional synthetic routes. These methods offer shorter reaction times, excellent yields, simple work-up procedures, and the use of green solvents or solvent-free and metal-free reaction conditions, making them more attractive from a green chemistry perspective. Moreover, microwave heating simplifies the solid-phase synthesis of disulfide-rich peptides, making it more viable, selective, and cost-effective. Notably, substantial progress has been made over the past two decades in synthesizing small molecules of both symmetrical and unsymmetrical organic sulfides and disulfides, including disulfide-containing therapeutic peptides, under microwave irradiation. This review provides an overview of recent advancements in the microwave-assisted synthesis of a wide variety of bioactive diaryl and aryl–alkyl sulfides and disulfides, including a disulfide-bridged cycloheptapeptide, along with critical discussions where necessary.
The objective of this review is to explore the role of Micro-wave-Assisted Synthesis (MAS) for the efficient and eco-friendly synthesis of heterocyclic compounds, which are critical scaffolds in drug discovery. The review highlights how MAS aligns with green chemistry principles by reducing reaction time, enhancing yields, and mini-mizing solvent use. It particularly focuses on the synthesis of bioactive heterocycles, including pyrimidines, quinolines, imidazoles, and indoles. A comprehensive literature review was conducted to analyze studies involving MAS in the synthesis of heterocyclic compounds. The methodology involved comparing microwave-based synthetic protocols with conventional methods based on parameters such as reaction time, yield, solvent usage, selectivity, and scalability. Recent technological advances, including con-tinuous-flow microwave reactors and AI-assisted optimization techniques, were also evaluated for their role in overcoming existing limitations. The studies reviewed consistently demonstrated that MAS significantly reduces reac-tion times (from hours to minutes), increases product yields, and improves selectivity compared to traditional thermal methods. For example, several heterocyclic compounds showed yield im-provements of over 20–30% when synthesized under microwave conditions. Additionally, MAS contributed to reduced solvent consumption, supporting environmentally sustainable practices. However, challenges related to industrial scalability and high equipment costs were noted. Microwave-assisted synthesis represents a powerful, sustainable, and time-effi-cient technique for the synthesis of pharmacologically important heterocycles. Despite limita-tions in scale-up and equipment accessibility, ongoing innovations—such as continuous-flow systems and AI-guided optimization—are addressing these barriers. MAS is expected to become increasingly vital in the future of drug discovery, offering a green alternative to conventional synthesis.
