Small cell-permeable natural products and their analogs play a crucial role in the treatment of disease. This proposal addresses the syntheses of several biologically active molecules relevant to the treatment of cancer, HIV, stroke and heart disease through """"""""The Synthesis and Application of Chiral Cyclohexadienones."""""""" Optically enriched chiral cyclohexadienones are relatively inaccessible chemical entities. Their fragile nature coupled with the lack of enantioselective access has hampered their widespread synthetic applications. We intend to show that robust cyclohexadienones can be constructed to undergo a myriad of diastereoselective reactions including 1,2-, 1,4- and 1,6-additions, along with various rearrangements and cycloadditions. We intend to prove that these cyclohexadienones can be easily constructed in enantiopure form. We will establish the usefulness of these adducts as non-racemic cyclohexyl synthons through short syntheses to ascertain the subtleties of the surrounding synthetic chemistry. Each proposed synthesis addresses a target that is (or has proven to be) difficult to construct by current technologies and is highly relevant to national public health. It should become evident that the synthetic method proposed has eventual greater application in the assembly of future prospective drugs.
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| David, Jonathan G; Bai, Wen-Ju; Weaver, Marisa G et al. (2014) A general diastereoselective catalytic vinylogous aldol reaction among tetramic acid-derived pyrroles. Org Lett 16:4384-7 |
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| Green, Jason C; Burnett 4th, G Leslie; Pettus, Thomas R R (2012) New strategies for natural products containing chroman spiroketals. Pure Appl Chem 84:1621-1631 |
| Wu, Kun-Liang; Mercado, Eduardo V; Pettus, Thomas R R (2011) A convergent total synthesis of (±)-?-rubromycin. J Am Chem Soc 133:6114-7 |
| Cha, Jacob Y; Burnett 4th, G Leslie; Huang, Yaodong et al. (2011) A strategy for the late-stage divergent syntheses of scyphostatin analogues. J Org Chem 76:1361-71 |
| Wenderski, Todd A; Marsini, Maurice A; Pettus, Thomas R R (2011) A diastereoselective formal synthesis of berkelic acid. Org Lett 13:118-21 |
| Wenderski, Todd A; Hoarau, Christophe; Mejorado, Lupe et al. (2010) Dearomatization applications of I((III)) reagents and some unusual reactivity amongst resorcinol derived cyclohexadienones. Tetrahedron 66:5873-5883 |
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