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.

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A stereoselective synthesis of the marine natural products, polyandrocarpamines A and B, has been achieved using a high-yielding one-step aldol condensation reaction under microwave conditions. The structures of both synthetic compounds were confirmed following 1D and 2D NMR, UV, IR and MS spectral analysis, and by comparison with literature data. Both synthetic natural products were assigned Z geometry about their exocyclic double bond on the basis of 13 C/ 1 H long-range coupling constants, which were measured using a gHSQMBC experiment. Polyandrocarpamines A and B were evaluated for their cytotoxicity towards the tumour cell lines, MCF-7 (breast), H460 (lung) and SF268 (central nervous system). Polyandrocarpamine A displayed selective cytotoxicity towards the SF268 cell line with a GI 50 value of 65 µM.

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