ABSTRACT
This chapter illustrates the approaches for the construction of natural product-like combinatorial libraries. The structural diversity, wide range of biological properties, and pharmacological profiles displayed by natural products, in addition to their dominant role in the discovery of leads for the development of drugs, constitute reasons for their integration in combinatorial drug design approaches. At one end of the spectrum of library design approaches is combinatorial semisynthesis using individual natural products as core scaffolds for derivatization in either solid or solution phase. A new and effective approach to combinatorial carbohydrate library generation for rapid ligand or receptor identification is dynamic combinatorial chemistry. The capacity of dynamic combinatorial chemistry to probe carbohydrate–protein interactions was also demonstrated with the glycosidase hen egg-white lysozyme. Examples of carbohydrate-based antibiotic libraries include aminoglycosides and glycopeptides. Moenomycins are a family of natural product antibiotics that are known to inhibit the synthesis of bacterial cell wall peptidoglycan through inhibition of transglycosylase.
