Asymmetric Total Synthesis of 5,10-seco-Neoansamycin A.

The first asymmetric total synthesis of 5,10-seco-neoansamycin A, a 19-membered cyclic octaketide, was achieved in 20 steps (with several steps being telescoped) and 6.7% overall yield starting from the reported compound, thus leading to the assignment of its absolute configuration. This convergent synthetic approach features late-stage macrolactamization, a judicious application of an asymmetric aldol reaction. This work will facilitate the synthesis of other ansamycin natural products and the explorations of 5,10-seco-neoansamycin A as a potential anticancer lead.