Quercetin: Synthesis Trends, Chemical Reactions, and Its Role as an Estrogen Receptor Alpha Modulator in Breast Cancer Therapy: A Systematic Literature Review

Quercetin, a flavonoid abundant in fruits and vegetables, has garnered significant attention for its therapeutic potential in breast cancer treatment. Despite its promising bioactivity, clinical applications of quercetin remain limited due to challenges in synthesis, structural stability, and bioavailability. This systematic review examines recent advancements in quercetin synthesis through diverse chemical reactions aimed at improving efficiency and pharmacological properties. Key strategies such as the Algar-Flynn-Oyamada reaction, regioselective esterification, and glycosylation are discussed alongside structural modifications like methylation and glycosylation to enhance chemical reactivity and bioactivity. The reviewed methods demonstrate notable progress in optimizing quercetin production and stability. Structural modifications have shown significant influence on the therapeutic efficacy of quercetin derivatives. However, challenges such as low yield and complex reaction conditions persist. Emerging approaches, including novel catalytic systems and sustainable synthetic methods, offer promising solutions for large-scale production. While substantial progress has been made in quercetin synthesis, further research is essential to refine existing methods and explore innovative strategies for improving reaction selectivity and scalability. Addressing these gaps will expand the application of quercetin in pharmaceutical and biomedical research, particularly in breast cancer therapy, paving the way for more effective treatments and improved patient outcomes. HIGHLIGHTS This review discusses the recent development of synthesis strategies for quercetin and its derivatives aimed at improving pharmacological potential and structural stability. The article highlights quercetin’s role as a modulator of Estrogen Receptor Alpha (ERα) and its therapeutic implications in breast cancer treatment. Key challenges in quercetin synthesis such as low bioavailability and yield are identified. The review introduces opportunities for future research in innovative synthetic methods and sustainable catalytic systems. Emphasis is placed on refining synthetic strategies to support the clinical application of quercetin-based therapeutics. GRAPHICAL ABSTRACT