The green chemistry of chalcones: Valuable sources of privileged core structures for drug discovery

Abstract

The sustainable use of resources is essential in all production areas, including pharmaceuticals. However, the aspect of sustainability needs to be taken into consideration not only in the production phase, but during the whole medicinal chemistry drug discovery trajectory. The continuous progress in the fields of green chemistry and the use of artificial intelligence are contributing to the speed and effectiveness of a more sustainable drug discovery pipeline. In this light, here we review the most recent sustainable and green synthetic approaches used for the preparation and derivatization of chalcones, an important class of privileged structures and building blocks used for the preparation of new biologically active compounds with a broad spectrum of potential therapeutic applications. The literature here reported has been retrieved from the SciFinder database using the term “chalcone” as a keyword and filtering the results applying the concept: “green chemistry”, and from the Reaxys database using the keywords “chalcone” and “green”. For both databases the time-frame was 2017–2022. References were manually selected based on relevance.

Design, synthesis and biological evaluation of novel pyrimidine derivatives as bone anabolic agents promoting osteogenesis via the BMP2/SMAD1 signaling pathway

“…There are several basic approaches towards the construction of a pyrimidine core, we have utilized chalcones (Scheme 1A) as a simple and economical synthon. 25 A series of unsymmetrical pyrimidines were synthesized by the cyclization of the respective chalcone (3) with guanidine hydrochloride (4) in the presence of NaOH in ethanol under reflux conditions for 24-48 hours and the obtained product upon crystallization provides pyrimidine derivatives 5a-5h (51-69% yields, Scheme 1A). At first, 2,4,5-tri-methoxy group (in ring A; electron-rich environment) and 4-halo group (in ring B) containing pyrimidines were synthesized with 51-58% yields (Scheme 1B, 5a-5c).…”

Antiviral and antimicrobial applications of chalcones and their derivatives: From nature to greener synthesis

“…Since the industrial production of these materials is of great importance, in order to obtain optimal conditions based on green chemistry principles, additional explorations should be conducted on synthesis strategies that are environmentally friendly, simple, cost-effective, and up-scalable. In this context, green catalysts and flow chemistry are among the introduced techniques with great potential for chalcone synthesis and its derivatization; however, limitations and challenges still exist regarding the generation of complex structures and the standardization and optimization of reaction/synthesis conditions, which warrant more in-depth analyses [ 39 ]. Generally, the synthesis of chalcones is conducted based on conventional Claisen-Schmidt condensation at high temperatures, but alternative approaches using green sources of energy, such as ultrasound and microwave, have been introduced.…”

“…Generally, the synthesis of chalcones is conducted based on conventional Claisen-Schmidt condensation at high temperatures, but alternative approaches using green sources of energy, such as ultrasound and microwave, have been introduced. In addition, the utilization of ionic liquids as catalysts can provide opportunities for solvent-free synthesis, thus enhancing the yield of production, shortening the operational processes, decreasing the formation of wastes, and reducing the reaction time [ 39 ].…”

Bibliometric Study of Microwave-Assisted Synthesis of Flavanone Derivatives

“…One of the most advanced, innovative, and environmentally friendly ways to obtain flavanone derivatives is to utilize microwaves using a microwave. Using a microwave can not only save material usage but can also shorten reaction time 6 . For example, our previous research 7 obtained prenyl derivatives from pinostrobin, a type of flavanone isolated from This study aims to describe various studies related to synthesizing flavanone derivatives using the microwave-assisted method with a bibliometric approach.…”