An overview of synthetic methodologies, bioactivity and molecular mechanisms of natural products

Bioactive natural products remain a premier source of lead scaffolds for drug discovery. This review integrates recent advances in the chemical synthesis, structural modification, pharmacological activities, and molecular mechanisms of natural products, with particular emphasis on linking structural optimization to pharmacological performance. Structurally, we systematically categorize major natural product classes including alkaloids, terpenoids, flavonoids, and polyphenols based on biosynthetic origins. Synthetically, we critically review milestone total and semi-synthetic strategies, state-of-the-art asymmetric catalysis, and modern green extraction techniques. Furthermore, we provide an in-depth analysis of molecular targets and mechanisms driving therapeutic effects, such as antitumor interventions, neuroprotection against ischemic stroke, multi-target antibacterial actions, and bone homeostasis regulation. By further correlating structural modifications with structure–activity relationships, we highlight how chemical optimization can influence pharmacological performance and discuss persistent challenges in synthetic efficiency, scalability, and material characterization, providing perspectives for natural-product-based drug design.