First Total Synthesis of the Marine-Derived Anti-inflammatory Natural Product (-)-Herdmanine D through a Steglich Esterification

An efficient and regioselective route for the first total synthesis of the antiinflammatory marine natural product (-)-herdmanine D, with an excellent overall yield of 18%, is described. A key feature of the synthetic strategy is a Steglich esterification of regioselectively constructed 6-bromo-5-methoxy-1 H -indole-3-carboxylic acid with protected l -tyrosine. The formation of the l -isomer was confirmed through measurement of the optical activity. The current strategy paves the way for the construction of diverse analogues of (-)-herdmanine D for drug development.