The goal of the proposed research is to develop an enantioselective synthesis of the antitumor alkaloid asparagamine A, which has been shown to have antitumor activity in vitro against a variety of tumor cell lines. MacMillan has recently developed the first organocatalytic, asymmetric Michael additions of pyrroles with alpha, beta- unsaturated aldehydes. Proposed herein is a novel extension to allow for the intervention of an aza-Prins cyclization of an iminium ion intermediate in the catalytic cycle. This will allow for a one-step synthesis of the core bridged pyrrolidine structure common to asparagamine A and stemofoline, a related alkaloid. The proposed synthesis is both novel and concise. Moreover, the proposed route will allow for the construction of analogs of the natural product that could be of significant medicinal value.
| Austin, Joel F; Kim, Sung-Gon; Sinz, Christopher J et al. (2004) Enantioselective organocatalytic construction of pyrroloindolines by a cascade addition-cyclization strategy: synthesis of (-)-flustramine B. Proc Natl Acad Sci U S A 101:5482-7 |
| Brown, Sean P; Brochu, Michael P; Sinz, Christopher J et al. (2003) The direct and enantioselective organocatalytic alpha-oxidation of aldehydes. J Am Chem Soc 125:10808-9 |
