Bioinspired Synthesis of Rearranged spiro-Lanostanes

Triterpenes are a rich class of natural products with diverse structures and biological activity. The more biologically and structurally interesting members of this family are often formed only in minute quantities or in protected species, which makes their accessibility by extraction from natural sources undesirable. In this project a subfamily of modified lanostane triterpenoids shall be rendered accessible from a biogenetically related natural product, lanosterol. To this end, chemical reactions that mimic the biosynthesis in plants will be developed, thus constituting a bioinspired synthesis. A key feature of the desired products is the rearranged carbon skeleton, which exhibits a 5,5-spirocyclic system instead of the 6,5-ring system usually present in steroids. Different methods for the construction of this spirocyclic structural motif will be explored. The products (and derivatives) of this synthetic campaign could find application in the realm of medicinal chemistry, as the primary targets Forrestiacids A and B showed potent ACL inhibition, an enzyme with relevance for LDL cholesterol and cancer.