Pseudo-Natural Products: Expanding chemical and biological space by surpassing natural constraints

This review explores the recent advancements in the design and synthesis of pseudo-natural products (pseudoNPs) by employing innovative principles and strategies, heralding a transformative era in chemistry and biology. Pseudo-NPs, produced through in silico fragmentation and the de novo recombination of natural product fragments, reveal compounds endowed with distinct biological activities. Their advantage lies in transcending natural product structures, fostering diverse possibilities. Research in this area over the past decade has yielded unconventional combinations of natural product fragments, leading to the identification of novel compounds possessing unique scaffolds and biological significance, thereby contributing to the discovery of new therapeutics. The pseudo-NPs exert potent biological effects through various signaling pathways. In chemical biology and medicinal chemistry, designing pseudo-NPs is an important strategy, harnessing molecular hybridization and bioinspired synthesis to generate diverse compounds with remarkable biological activities, underscoring their immense potential in drug discovery and development.