Pseudo Natural Products—Chemical Evolution of Natural Product Structure. (23rd March 2021)

• Record Type: Journal Article
• Authors: Karageorgis, George; Foley, Daniel J.; Laraia, Luca; Brakmann, Susanne; Waldmann, Herbert
• Is Part Of: Angewandte Chemie. Volume 133:Number 29(2021)
• Page Start: 15837
• Page End: 15855
• Publication Date: 2021-03-23
• Subjects: biological activity -- chemical biology -- fragment-based design -- natural products -- natural selection; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202016575
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Pseudo‐natural products (PNPs) combine natural product (NP) fragments in novel arrangements not accessible by current biosynthesis pathways. As such they can be regarded as non‐biogenic fusions of NP‐derived fragments. They inherit key biological characteristics of the guiding natural product, such as chemical and physiological properties, yet define small molecule chemotypes with unprecedented or unexpected bioactivity. We iterate the design principles underpinning PNP scaffolds and highlight their syntheses and biological investigations. We provide a cheminformatic analysis of PNP collections assessing their molecular properties and shape diversity. We propose and discuss how the iterative analysis of NP structure, design, synthesis, and biological evaluation of PNPs can be regarded as a human‐driven branch of the evolution of natural products, that is, a chemical evolution of natural product structure. Abstract : Pseudo‐natural products provide new opportunities in the discovery of bioactive small molecules and can be regarded as a human‐driven chemical evolution of natural product structure.