Total Synthesis of (±)-Englerin A and Its Tuncated Analogues

A convergent approach allowed total synthesis of (+/-)-Englerin A, and its truncated analogues, employing a thermal 1,3-dipolar cycloaddition of a highly substituted pyrylium ylide with vinyl acetate as the key step. The key intermediate, a 8-oxabicyclo[3,2,1]octane oxygenated at the C6 position, was directly converted into a truncated Englerin A analogue. Cu-I catalyzed conjugate addition of vinyl Grignard to an enone, ozonolysis, and epimerisation of the resulting aldehyde allowed stereoselective introduction of the side-chain leading to a total synthesis of the racemic natural product. The developed chemistry will allow synthesis of more complex analogues of the natural product based on the use of the key bicyclo[3,2,1]octane scaffold.