Building complexity is just about the most important thing when you’re making natural products. These molecules tend to have multiple stereocenters, and require elaborate multistep syntheses and catalysts to make in a laboratory. Chemists are always on the lookout for shorter, more efficient routes to natural products. Such advances could also improve methods for making drugs, agrochemicals, and materials. Now, Dirk Trauner and coworkers at New York University have synthesized preuisolactone A with a 57% yield in just three steps (J. Am. Chem. Soc. 2019, DOI: 10.1021/jacs.9b08892). The compound, which can be isolated from the fungus Preussia isomera, is a racemic mixture with seven adjacent stereocenters. Normally, making a molecule of this complexity would require a 20-step synthesis, Trauner says. Inspired by biosynthetic pathways for similar natural products, the group was able to show that the molecule comes together in three oxidative steps starting with a pair of achiral polyphenols. The researchers also showed that preuisolactone A is likely a polyketide and not a terpenoid as previously thought. The work shows the power of oxidative cascades to build very complex natural products, says David Sarlah, an organic chemist at the University of Illinois at Urbana-Champaign. “It does not get any shorter and sweeter than this,” Trauner says.