Leptospermone (Lep)

Leptospermone can be synthesized from phloroglucinol by a reaction with 3-methylbutanenitrile (isovaleronitrile) in the presence of a zinc chloride catalyst. Phluroisovalerone imine is produced which is then alkylated with iodomethane after initial treatment with sodium ethoxide and methanol to produce an intermediate which is treated with aqueous hydrochloric acid resulting in isovaleroylsyncarpic acid (leptospermone). Biochemically, the plants take a different approach. Despite the fact that the biochemical synthesis has not been specifically investigated, it is clear that leptospermone is not an oxidized terpene as the cyclisation of farnesyl pyrophosphate cannot produce two dimethylate carbons that are separated by a single carbon nor would this be consistent with the natural occurrence of similar compounds with different keto-aryl side-chains in the members of the Myrtaceae.