Finding small molecules that selectively modulate protein function remains one of the major challenges in the fields of chemogenomics and drug development. Natural products interact with proteins in their biosynthesis and when displaying biological activity, and can therefore be considered as "privileged structures". Thus, natural products may serve as biologically validated starting points for the design of focused compound collections. In recent years, effective synthesis methods for natural-product-based focused compound collections have been developed, including multi-component reactions. This review discusses recent advances in the synthesis of natural-product-inspired compound collections as well as the application of Protein Structure Similarity Clustering (PSSC) and a Structural Classification Of Natural Products (SCONP) as guiding principles for the design of focused compound collections based on natural products.

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