Chemists Collaborate To Make Citrinadin Alkaloids

For organic chemists seeking exciting molecules to work on, the fungal alkaloids known as citrinadins tick all the right boxes: myriad chiral centers, structural motifs common in pharmaceuticals, and activity against a human cancer cell line. But those chemists have been chasing the wrong molecules. Independent teams led by Stephen F. Martin of the University of Texas, Austin, and John L. Wood of Colorado State University have completed the first enantioselective total syntheses of citrinadins A and B, respectively. In back-to-back publications, they show that the original citrinadin stereochemistry, reported in 2004, was misassigned (J. Am. Chem. Soc. 2013, DOI: 10.1021/ja405547f and 10.1021/ja405548b). Martin and Wood learned they were working toward related molecules at a conference and exchanged some information thereafter. For instance, Wood gave the Martin lab suggestions for introducing the citrinadins’ epoxy ketone moiety. Each lab had its own citrinadin approach, with Martin’s using an enantioselective vinylogous Mannich reaction and Wood’s using nitrone cycloadditions. The work comes from “titans in synthesis,” says Richmond Sarpong of the University of California, Berkeley, whose lab is working toward related molecules, “so the impressive creativity on display is no surprise.”