Application of a microwave assisted aza-Cope rearrangement--Mannich reaction to the synthesis of pyrrolizidine alkaloids

CHED 349

Amanda M. Schalk, aschalk@emich.edu, Patricia T. Sinawe, psinawe@emich.edu, Wesley A. Turley, wturley@emich.edu, and Harriet A. Lindsay, hlindsay@emich.edu. Department of Chemistry, Eastern Michigan University, 225 Mark Jefferson, Ypsilanti, MI 48197
Alexine and related alkaloids that are structurally similar to sugars are attractive as targets for total synthesis because many have demonstrated the ability to inhibit glycosidases. In efforts directed toward synthesizing certain natural and unnatural pyrrolizidine alkaloids, we are employing a stereoselective aza-Cope reaction—Mannich cyclization to construct the bicyclic core and install as many as three contiguous stereocenters. One limitation of the aza-Cope—Mannich reaction is that it typically requires long reaction times. In our laboratory we have been addressing this issue by investigating the use of microwave energy as a means to accelerate the reaction. Synthesis of the second generation of reaction precursors, efforts toward optimizing the conditions of the microwave-assisted aza-Cope—Mannich reaction, and stereoselectivity in the reaction will be discussed.