Ophiobolin sesterterpenes are a family of fungal metabolites that have been shown to have cancer-killing properties, even against the drug-resistant brain tumor glioblastoma multiforme. As targets for total synthesis, they pose plenty of challenges for organic chemists: They’re packed with stereocenters and feature a 5-8-5 fused ring system that’s tough to construct. Previous efforts have produced ophiobolin A in 47 steps and ophiobolin C in 38 steps. Chemists at the University of California, Berkeley, have now managed to make another family member, (–)-6-epi-ophiobolin N, in just nine steps, starting from farnesol (Science 2016, DOI: 10.1126/science.aaf6742). The key process in the synthetic route, developed by Thomas J. Maimone, Zachary G. Brill, and Huck K. Grover, is a radical cascade reaction that knits together the 5-8-5 fused ring system. When the researchers first tried this radical reaction, they found it gave them a mix of stereoisomers at one carbon, with the majority of the product having the undesired stereochemistry. After some trial and error, they found that addition of a complex thiol could shift the stereochemical outcome to produce more of the desired product. The researchers say this work lays the foundation for forging other complex ring systems that could benefit total syntheses.