Progress toward the asymmetric total synthesis of (-)-mucocin

ORGN 181

Yan Zhang, yanzhang@email.unc.edu1, Michael T. Crimmins1, and Frank A. Diaz2. (1) Department of Chemistry, University of North Carolina at Chapel Hill, Campus Box #3290, Chapel Hill, NC 27599, (2) Icos Corporation, Bothell, WA
Mucocin, a member of the anonnaceous acetogenin family, was first isolated from the leaves of Rollinia mucosa in 1995. The unique structure of this compound and its potent antitumor activity against A-549 (lung cancer) and PACA-2 (pancreatic cancer) tumor cell lines have elicited significant synthetic interest. Our approach for the construction of both the tetrahydrofuran (THF) and the tetrahydropyran (THP) fragments relies on the asymmetric glycolate aldol-ring closing metathesis (RCM) methodology developed in our laboratory. A cross metathesis strategy is then utilized as the key step to couple these two advanced synthetic intermediates. Recent progress toward the completion of the total synthesis of this natural product will be discussed.