The peptide natural product yaku'amide A (1) is a potent anticancer agent with a novel mechanism of action. Inoue et al. recently established that 1 both inhibits ATP production and enhances ATP hydrolysis. The total synthesis of 1 is lengthy due to the presence of challenging E- and Z-dehydroisoleucine residues. Replacing these amino acids with either dehydrovaline or dehydronorvaline would significantly simplify the synthetic route to 1. Our computation studies indicated that analogues 1a and 1b, which contain these symmetrical dehydroamino acids, closely mimic the three-dimensional structure of 1. This presentation will summarize our total synthesis of 1 as well as the shorter routes to 1a and 1b.

Progress towards the total synthesis of yaku'amide A and analogues

2019 Fall National Meeting

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