New Cyclization Mechanism for Squalene: a Ring-expansion Step for the Five-membered C-ring Intermediate in Hopene Biosynthesis

Three triterpenes having the 6/6/5-fused tri- and 6/6/6/5-fused tetracyclic skeletons were isolated from an incubation mixture of the mutated F601A enzyme, these products being in accordance with a Markovnikov closure. Successful trapping of the tricyclic cationic intermediate by using the squalene analog having a highly nucleophilic hydroxyl group leads us to propose that the ring expansion process of the 5-membered C-ring is involved in the squalene cyclization cascade.