Natural Products Research and Development: Applications, Advanced Analytical Approaches, Sustainable Extraction, and Drug Development Strategies
María del Carmen Castillejos, Laura Guerrero Molina, Rosa M. Sanchez-Garcia, Maria Luisa Castejón, Jenifer SantosNatural products represent a major source of structurally diverse bioactive compounds with applications in pharmaceutical, nutraceutical, cosmetic, agricultural, and other industrial sectors. Despite the extensive literature in this field, existing reviews frequently address biological applications, extraction technologies, analytical characterization, or drug-development strategies as separate research areas, limiting an integrated understanding of how advances across these stages collectively influence natural-product discovery and translation. This review addresses this gap by providing a multidisciplinary perspective that connects natural-product sources and applications with sustainable extraction, advanced analytical characterization, data-driven approaches, and emerging drug-development strategies. Particular attention is given to green and intensified extraction technologies, including supercritical fluid, ultrasound-assisted, microwave-assisted, pressurized-liquid, enzyme-assisted extraction, and natural deep eutectic solvents, together with their efficiency, sustainability, and scalability. Advances in chromatography, high-resolution mass spectrometry, nuclear magnetic resonance, metabolomics, molecular networking, and artificial intelligence-assisted data analysis are critically discussed as tools for improving compound identification, prioritization, and biological interpretation. Furthermore, emerging synthetic and semisynthetic strategies, including late-stage functionalization, biocatalysis, synthetic biology, and continuous-flow processing, are examined in relation to molecular optimization and scalable production. Current limitations concerning standardization, toxicological assessment, regulatory requirements, industrial scalability, and translation are also considered. Overall, this review highlights the need to integrate these traditionally fragmented areas into a coherent natural-product research and development pipeline to improve reproducibility, sustainability, and successful translation into practical applications.