The long-term objective of the proposed research is to develop novel methodology that will facilitate the synthesis of pharmacologically-interesting natural and non-natural alkaloids. Specifically, the proposal describes the development of two new sequenced reactions that are initiated by the formation of iminium ion intermediates. If successful the methodology will provide a route to topologically complex heterocycles from readily available aldimines and ketimines. Rapid access to the appropriate model systems via known methods will allow the ready asessment of the feasibility and efficiency of the proposed reactions. The model systems will then be extended toa general and enantioselective synthesis of 2,6-disubstituted heterocyles. Finally, the proposal outlines the asymmetric total synthesis of the neurotransmission inhibiting indolizidine alkaloid (+)-Indolizidine 209D, the antimicrobial indolizidine alkaloid Piclavine A1, and the structurally interesting toxic alkaloid Pumiliotoxin C via the proposed reactions.
| Amorde, Shawn M; Judd, Andrew S; Martin, Stephen F (2005) Cascade iminium ion reactions for the facile synthesis of quinolizidines. Concise syntheses of (+/-)-epilupinine and (-)-epimyrtine. Org Lett 7:2031-3 |
| Hergenrother, Paul J; Hodgson, Anne; Judd, Andrew S et al. (2003) An abiotic strategy for the enantioselective synthesis of erythromycin B. Angew Chem Int Ed Engl 42:3278-81 |
