Asymmetric Total Synthesis and Biosynthetic Implications of Perovskones, Hydrangenone, and Hydrangenone B

Perovskones and hydrangenones are a family of structurally complex triterpenoids that were mainly isolated from the genus Salvia medicinal plants. These isoprenoids exhibit a broad range of biological activities, such as antitumor and antiplasmodial activities. Here, we report the collective total synthesis of perovskone, perovskones C, D, F, hydrangenone, and hydrangenone B. The key strategies in this work include the following: (1) an asymmetric photoenolization/Diels-Alder reaction was developed to construct a tricyclic ring bearing three contiguous quaternary centers, which was used to build the core icetexane skeleton; (2) a bioinspired Diels-Alder reaction of perovskatone D with trans-alpha-ocimene was applied to stereospecifically generate perovskones; (3) late-stage oxidations and ring forming steps were developed to synthesize perovskones and hydrangenones. Our synthetic work suggests that (1) perovskatone D may serve as the precursor of the biosynthesis of perovskones and (2) the formation of hydrangenone and hydrangenone B, containing a five-membered D ring, may involve an oxidative ring cleavage and ring regeneration process.

Automated summary

Perovskones and hydrangenones are a family of structurally complex triterpenoids mainly isolated from Salvia medicinal plants, showing a wide range of biological activities such as antitumor and antiplasmodial activities. The total synthesis of these compounds involved asymmetric photoenolization/Diels-Alder reactions, bioinspired Diels-Alder reactions, and late-stage oxidations and ring forming steps. Studies suggest that perovskatone D may be a precursor for the biosynthesis of perovskones, while the formation of hydrangenone and hydrangenone B may involve an oxidative ring cleavage and ring regeneration process.