Part I: Studies toward the total synthesis of Trocheliophorolide A. Part II: Studies on the development of a palladium-catalyzed carbonylative cross-coupling towards the synthesis of alkenyl alkynyl ketones.

William T. Spencer III


In Part I, efforts toward the total synthesis of a novel antibacterial y-lactone, Trocheliophorolide A, are described. The natural product was isolated from Red Sea soft corals S. trocheliophorum and L. arboreum. Biological assays show that this compound exhibits significant growth inhibition of bacterial cell lines S. aureus and B. subtilis. The structure consists of an (S)-β-angelica lactone ring connected to an ynediene side chain. Our strategy employs synthesis of the lactone ring as a stannylfuranone, which will be Stille coupled with vinylidene dibromide to form an alkenyl bromide. This alkenyl bromide will be cross-coupled with an enynyl metal species to install the remainder of the sidechain, affording the target natural product. The stannylfuranone ring was constructed using a tandem palladium-catalyzed hydrostannation-lactonization protocol. In Part II, a study towards the synthesis of alkenyl alkynyl ketones via a novel palladium-catalyzed carbonylative cross-coupling reaction of alkynyl halides and alkenylstannanes is discussed. Initial efforts have focused on optimization of the direct cross-coupling of the two components in the absence of carbon monoxide pressure antecedent to development of the carbonylative coupling reaction.