Members of a recently discovered family of aminoguanidine-containing marine natural products, the clavatadines, have been targets of interest due to their intriguing structure and relatively unexplored biological activity profile. Clavatadine A and B are specific inhibitors of human blood coagulation factor XIa. Although clavatadine C, D, and E do not bind selectively to factor XIa, derivatives of clavatadine C have been investigated as potential anticancer agents. Meanwhile, the bioactivity spectrum of clavatadine D and E remains wholly unknown.<br/><br/>The first total syntheses of clavatadine D and E, and the second total synthesis of clavatadine C were completed by one undergraduate student and the PI at a teaching-intensive, primarily undergraduate institution. Clavatadine C, D, and E were each prepared in five steps from esters of L-tyrosine using a late-stage amide-coupling strategy, and each synthesis featured minimal use of protecting groups. For example, an unprotected phenol and oxime were merely spectators during the synthesis of clavatadine E. The convergent nature of the synthetic approach is readily amenable to analogue preparation. Preliminary efforts to uncover the biological activity of these natural products will also be presented.

Total synthesis of clavatadines C–E

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.