Addressing drug-like/lead-like properties of biologically active small molecules early in a lead generation program is the current paradigm within the drug discovery community. Lipinski's "rule of five" has become the most commonly used tool to assess the relationship between structures and drug-like properties. Sixty percent of the 126 140 unique compounds in The Dictionary of Natural Products had no violations of Lipinski's "rule of five". We have isolated 814 natural products based on their expected drug-like/lead-like properties to generate a natural product library (NPL) in which 85% of the isolated compounds had no Lipinski violations. The library demonstrates the feasibility of obtaining natural products known for rich chemical diversity with the required physicochemical properties for drug discovery. The knowledge generated in creation of the library of structurally characterized pure natural products may provide opportunities to front-load lead-like property space in natural product drug discovery programs.