Total synthesis of (±)-hyphodermins A and D

Article abstract of DOI:10.1021/jo800227p

(Chemical Equation Presented) An efficient formal synthesis of (±)-hyphodermins A and D, metabolites of Hyphoderma radula, has been completed in 12 and 11 steps, respectively. The tricyclic carbon skeleton of enone 6 was rapidly assembled from diester 11 via an α brominationn - elimination sequence followed by anhydride formation. Regioselective reduction of the lactone group of enone 6 with LiA1H(t-BuO)₃ gave lactol 15. Lactol 15 was converted in two steps to (±)-hyphodermin D, without the need for complex protection-deprotection strategies. Lactol 15 was converted in three steps to (±)-hyphodermin A, via the key step of epoxidation of an enone in the presence of a THP lactol. A combination of NMR and ab initio studies suggests that the structures of hyphodermin C and D should be interchanged.