| Two approaches towards the total synthesis of uprolide-D will be described. The first of these is a linear approach whereby new methodology was developed for formation of the embedded 2,5-disubstituted tetrahydrofuran ring by stereospecific elimination cyclization of 1-iodomethyl-1,5-bis-epoxides. Chiral allenyl metal methodology will be employed to assemble the C12-C13-C14-C1 stereotetrad array. Following failure of this first approach, a second effort was undertaken which not only took advantage of the chiral allenyl metal methodology and stereospecific elimination-cyclization sequence to form the embedded tetrahydrofuran ring, but also incorporated a convergent approach to the uprolide-D carbon skeleton. |
