This proposal is divided into three subsections that are unified by the theme of using new sequences of radical reactions as key steps in the synthesis of important natural products. 1) Camptothecin: The camptothecins are among the most promising chemotherapeutic agents under development for treatment of cancer, and recently there are indications that they may represent new directions in antiretroviral (AIDS) chemotherapy. Development of an efficient total synthesis of (S)-camptothecin and its relatives is proposed. The key step is a new 4 + 1 radical annulation for the synthesis of pyrroloisoquinolines. Long range goals include the preparation of gram-quantities of important existing camptothecins and the synthesis of new analogs for testing. 2) Crinipellin: The crinipellins are a small family of tetraquinanes with antibiotic activity. The immediate goal of this project is to develop a synthesis of optically active crinipellin A by using a new type of tandem cyclization as the central reaction. Long range goals include the study of diastereoselective radical additions to dienes. 3) Steroids: The goal of this project is to develop a strategically new approach to the steroid ring system. Experiments are planned to test the idea that a macrocyclization can be followed by three successive transannular cyclizations, resulting in a one step synthesis of the steroid nucleus from acyclic precursors. A key feature of this strategy is the question of whether the conformation of the macrocyclic radicals can control the stereochemistry of the ring fusions in the transannular cyclizations.
| Moretti, Jared D; Wang, Xiao; Curran, Dennis P (2012) Minimal fluorous tagging strategy that enables the synthesis of the complete stereoisomer library of SCH725674 macrolactones. J Am Chem Soc 134:7963-70 |
| Gudipati, Venugopal; Curran, Dennis P (2011) Synthesis of C1-C20 and C21-C40 fragments of tetrafibricin. Tetrahedron Lett 52:2254-2257 |
| Moura-Letts, Gustavo; Curran, Dennis P (2007) Selective synthesis of (2Z,4E)-dienyl esters by ene-diene cross metathesis. Org Lett 9:5-8 |
| Du, Wu; Curran, Dennis P; Bevins, Robert L et al. (2002) Synthesis and evaluation of a novel E-ring modified alpha-hydroxy keto ether analogue of camptothecin. Bioorg Med Chem 10:103-10 |
