摘要Natural products(NPs)are invaluable resources for drug discovery,characterized by their intricate scaffolds and diverse bioactivities.Al drug discovery&design(AIDD)has emerged as a transformative approach for the rational structural modification of NPs.This review examines a variety of molecular generation models since 2020,focusing on their potential applications in two primary scenarios of NPs structure modification:modifications when the target is identified and when it remains unidentified.Most of the molecular generative models discussed herein are open-source,and their applicability across different domains and technical feasibility have been evaluated.This evaluation was accomplished by integrating a limited number of research cases and successful practices observed in the molec-ular optimization of synthetic compounds.Furthermore,the challenges and prospects of employing molecular generation modeling for the structural modification of NPs are discussed.