Concise Synthesis Of (+)-[C-13(4)]-Anatoxin-A By Dynamic Kinetic Resolution Of A Cyclic Iminium Ion

An asymmetric total synthesis of [C-13(4)]-anatoxin-a ([C-13(4)]-1) has been developed from commercially available ethyl [C-13(4)]-acetoacetate ([C-13(4)]-15). The unique requirements associated with isotope incorporation inspired a new, robust, and highly scalable route, providing access to 0.110 g of this internal standard for use in the detection and precise quantification of anatoxin-a in freshwater. A highlight of the synthesis is a method that leverages a cyclic iminium ion racemization to achieve dynamic kinetic resolution in an enantioselective Morita-Baylis-Hillman (MBH) cyclization.