Total Synthesis of a Nonclassical Bioactive Acetogenin, (+)-Muconin

A convergent total synthesis of the tetrahydropyran-bearing acetogenin (+)-muconin 1 is described. All five chiral building blocks 7, 9, 17, 21, and 29 were prepared from d-glutamic acid, respectively. Four out of them were used to furnish the alkyne 16 and the iodoalkyne 33, respectively, and palladium(0)-mediated cross-coupling of alkynes 16 and 33, followed by hydrogenation, afforded 36. Simultaneous deprotection of the MOM and TBS groups in 36 with BF3·Et2O in the presence of Me2S provided (+)-muconin 1.