Ocean-dwelling sponges produce molecules complex enough to intimidate the boldest of organic chemists. And they may be even more skilled in synthesis than researchers thought: A new study demonstrates that three related sponge alkaloids—sceptrin, ageliferin, and massadine—have mismatched chirality, in contrast to prior reports (Science 2014, DOI: 10.1126/science.1255677). Most natural product families include members that all have the same chirality or are all mixtures, explains Chuo Chen of the University of Texas Southwestern Medical Center, who led the research. Chen made the mismatch discovery after synthesizing and crystallizing sceptrin and ageliferin in collaboration with Phil S. Baran of Scripps Research Institute California and Arnold L. Rheingold of the University of California, San Diego. The trio obtained the opposite stereochemistry compared with natural samples, which led them to conclude that sceptrin and ageliferin’s absolute stereochemistry is different from massadine’s and had originally been misassigned. It’s not yet clear how the sponge achieves this divergence in chirality, Chen says. He notes that the team made sceptrin and ageliferin with oxidative reactions that other chemists have postulated are involved in their biosynthesis, including single-electron transfer, so this work provides more support for those biosynthesis pathways in addition to revealing the chirality mismatch.