The aim of the proposal is the application of novel intramolecular acyl radical cyclizations to the synthesis of biologically important cyclic ethers. Although numerous methods exist for the synthesis of these compounds, the search for new methods with increased skeletal and stereochemical flexibility continues. Acyl radicals have received relatively limited attention as reactive intermediates in organic synthesis, despite their potential to efficiently form carbon-carbon bonds. The PI's preliminary synthetic studies indicate that this methodology is likely to have significant utility for target directed synthesis. The synthetic studies proposed herein will focus on the preparation of cis-kumausyne, kumausallene, and the development of a viable strategy for the potent antifungal agents gamberic acids A-D. The gamberic acids A-D represent the most potent antifungal agents known, with activity exceeding that of amphotericin B by over three orders of magnitude, making them extremely important targets.
| Evans, P Andrew; Grisin, Aleksandr; Lawler, Michael J (2012) Diastereoselective construction of syn-1,3-dioxanes via a bismuth-mediated two-component hemiacetal/oxa-conjugate addition reaction. J Am Chem Soc 134:2856-9 |
| Evans, P Andrew; Sawyer, James R; Inglesby, Phillip A (2010) Regiodivergent ligand-controlled rhodium-catalyzed [(2+2)+2] carbocyclization reactions with alkyl substituted methyl propiolates. Angew Chem Int Ed Engl 49:5746-9 |
