A formal synthesis of (+)-pyripyropene A using a biomimetic epoxy-olefin cyclisation: effect of epoxy alcohol/ether on cyclisation efficiency

Abstract

The synthesis of the decalin sub-unit 2 of (+)-pyripyropene A 1 (a key intermediate in the first total synthesis) is described. The key step involves a biomimetic epoxy-olefin cyclisation using an allylsilane as the terminating group. Whilst attempts to cyclise epoxy alcohol 6 were unfruitful, cyclisation of the protected epoxy benzyl ether 7 using BF₃·OEt₂ was successful, yielding bicyclic ester 25. Isomerisation of the exocyclic double bond into conjugation with the ester group proved to be problematic, although successful conditions were ultimately found.