Abstract by Concordia Lo
Chemistry and Biochemistry
Progress Towards the Total Synthesis of Yaku\'amide A
Yaku’amide A (YA) is a rare peptide that exhibits potent anticancer activity against P388 murine leukemia cells (IC50 = 14 ng/mL). Furthermore, its anticancer profile in the JFCR39 panel of cancer cell lines revealed a novel and unique mode of action. Unfortunately, due to its scarcity in nature, comprehensive biological studies have remained elusive. The structure of YA contains complex unsymmetrical bulky dehydroamino acids such as E- and Z- dehydroisoleucine, which pose a synthetic challenge. Using a one-pot reaction involving an anti-dehydration, azide reduction, and an OàN acyl transfer to construct these stereospecific residues, we report an efficient and convergent synthesis of this natural peptide involving a total of 64 steps.