Asymmetric total synthesis of apratoxin D

The first asymmetric total synthesis of the marine natural product apratoxin D, a highly potent inhibitor of H-460 human lung cancer cell growth (IC(50) value of 2.6 nM), is described. Asymmetric N-amino cyclic carbamate (ACC) α,α-bisalkylation was utilized to establish the isolated C-37 methyl group with excellent selectivity. Other key asymmetric transformations employed were an Evans syn-aldol and a Paterson anti-aldol, both of which also proceeded with excellent stereoselectivity.