This proposal sets forth a research program for the development of new organic reactions involving chiral allenylcarbonyl compounds that aims to facilitate the synthesis of pyran bicyclic natural products. Numerous compounds containing the pyran ring exhibit important biological activity against tumors, HIV infection, and inflammation. To explore the medicinal potential of various important members of the family of pyran natural products, an innovative and general strategy for their chemical synthesis is proposed. Specifically, the synthesis of three pyran-containing compounds is discussed - harpagide, an anti-inflammatory compound, and two simplified analogs of ochrephilone, an anti-HIV agent. The projected route for the synthesis ochrephilone analogs and harpagide involves the development of three new reactions, the first being a powerful intramolecular Diels-Alder cyclization. Preliminary data included in the proposal demonstrate, for the first time, the feasibility of Diels-Alder reactions of allenyl carbonyl groups (as diene equivalents) with vinylselenium dienophiles. The second reaction targeted in this proposal involves the formation of vinylselenium compounds with control over the double-bond geometry. Thirdly, a novel manganese complexation/rearrangement reaction to give non-racemic allenyl carbonyl compounds is described. Besides their application in this proposed work, these three key reactions taken together are also expected to facilitate the future synthesis of a wide variety pyran bicyclic compounds.
| Maity, Pradip; Lepore, Salvatore D (2009) Selective one-pot synthesis of allenyl and alkynyl esters from beta-ketoesters. J Org Chem 74:158-62 |
| Maity, Pradip; Lepore, Salvatore D (2009) Anion-catalyzed addition of gamma-silylallenyl esters to aldehydes: a new entry into [3.2.1] bicyclic natural products. J Am Chem Soc 131:4196-7 |
| Silvestri, Maximilian A; Bromfield, Deborah C; Lepore, Salvatore D (2005) Michael-Stork addition of cyclopentyl enamine to allenyl ketones and esters. J Org Chem 70:8239-41 |
| Lepore, Salvatore D; He, Yuanjun (2005) Deconjugative conversion of alpha-alkynyl esters to alpha,alpha-disubstituted beta-alkynyl esters. J Org Chem 70:4546-8 |
| Lepore, Salvatore D; He, Yuanjun; Damisse, Pamela (2004) Studies on the base-promoted conversion of conjugated alkynyl esters to alpha-substituted alpha-allenyl esters. J Org Chem 69:9171-5 |
