Total Synthesis of (-)-Enigmazole B

Total synthesis of (-)-enigmazole B was achieved for the first time. Highlights of the present synthesis include an olefin cross-metathesis and hemiacetalization/intramolecular oxa-Michael addition sequence for accessing an (E)-configured enol tosylate, a Sonogashira cross-coupling to assemble all the carbon atoms of the target natural product, a remarkably chemo- and regioselective Au-catalyzed intramolecular alkyne hydroalkoxylation for the construction of the dihydropyran ring, and a Yamaguchi macrolactonization to close the 18-membered macrolactone skeleton.

Automated summary

The total synthesis of (-)-enigmazole B was achieved for the first time using a series of efficient chemical reactions, including olefin cross-metathesis, hemiacetalization/intramolecular oxa-Michael addition sequence, Sonogashira cross-coupling, chemo- and regioselective Au-catalyzed intramolecular alkyne hydroalkoxylation, and Yamaguchi macrolactonization.