Total Synthesis of (-)-Levesquamide

J Org Chem. 2023 Mar 17;88(6):3981-3986. doi: 10.1021/acs.joc.2c03066. Epub 2023 Mar 2.


The total synthesis of levesquamide, a natural product with an unprecedented pentasubstituted pyridine-isothiazolinone skeleton, has been accomplished from kojic acid for the first time. The key features of the synthesis include a Suzuki coupling reaction between bromopyranone and oxazolyl borate fragments, a copper-mediated introduction of a thioether, a mild hydrolysis of a pyridine 2-N-methoxyamide, and a Pummerer-type cyclization of a tert-butyl sulfoxide to form the key pyridine-isothiazolinone unit of the natural product.