Routes to nine-membered enediynes: not such a walk in the park

<p>The kedarcidin and C1027 chromophores are formidable targets for total synthesis. In this talk, I will describe viable routes to these highly unstable natural products. Over 20-years during our study of these nine-membered enediyne chromophores, several new methods may now be highlighted: stereoselective epoxyalkyne formation, atropselective Pd/Cu-Sonogashira coupling, 2-deoxy-?-glycosylation, CeX3-mediated enediyne cyclisation, and SmI2-based reductive olefination.Further application of these methods to the biomimetic study of the putative enediyne-precursors of the cyanosporasides, sporolides, and fijiolides will also be presented. In particular, I will present biomimetic evidence of a p-benzyne diradical species reacting in either a radical mode (hydrogen abstraction) or ionic mode (chloride attack) at the same sterically exposed site, leading to either monochlorinated cyanosporaside A or cyanosporaside B, respectively. The ionic monochlorination of the cycloaromatized p-benzyne of the C1027 enediyne core to generate the fijiolide aglycon framework will also be disclosed for the first time (unpublished work).</p>