Concise Synthesis of (+)-[13 C4 ]-Anatoxin-a by Dynamic Kinetic Resolution of a Cyclic Iminium Ion

Abstract

An asymmetric total synthesis of [¹³ C₄ ]-anatoxin-a ([¹³ C₄ ]-1) has been developed from commercially available ethyl [¹³ C₄ ]-acetoacetate ([¹³ C₄ ]-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.

Keywords: cyclization; isotopes; natural products; rearrangements; total synthesis.