A new diversity-oriented synthesis approach can create natural-product-like compounds with a uniquely wide range of basic framework structures, according to its creators (Angew. Chem. Int. Ed., DOI: 10.1002/anie.200804486). Scientists would like to be able to conveniently synthesize libraries of small organic molecules with a broad variety of structures like those found in natural products—including complex ring systems, intramolecular hydrogen bonding, unsaturation, and dense substitution—so the compounds can be screened as drug candidates and for other uses. Previous techniques have made it possible to produce compound libraries with up to 30 different frameworks per synthesis, but the new approach yielded 84 frameworks, reports chemical biology professor Adam Nelson of the University of Leeds, in England, who led the team that developed it. "The key to our approach," Nelson and coworkers note, "was the extraordinary scope of ring-closing metathesis." It acts like a scaffold-reprogramming reaction to define a wide range of frameworks in the final compounds. "Many of the diverse scaffolds prepared have scope for easy further diversification, which may allow the discovery of novel bioactive small-molecule tools," Nelson and his team write.