Stereoselective total synthesis of the marine sesterterpenoid (±)-palauolide

Abstract

A total synthesis of the antimicrobial, structurally unusual sesterterpenoid (±)-palauolide (1) is described. Methylenecyclohexane annulation of 3,6-dimethyl-2-cyclohexen-1-one (4) afforded a mixture of the bicyclic ketones 7 and 9 in a ratio of 94:6. Stereoselective conversion of this mixture into the phosphorodiamidate 46 was achieved via a five-step reaction sequence. Reduction of 46 with Li in MeNH2 gave the bicyclic substance 47, which was readily transformed in seven steps into the α,β-unsaturated aldehyde 54. Subjection of 54 to a Julia olefin synthesis, employing reagent 56, gave the furan 58. Photooxygenation of 58 provided (±)-palauolide (1).