Kanamienamide is a novel enol ether containing enamide with a single digit micromolar inhibitory activity against cancer cell lines. An efficient and convergent total synthesis of kanamienamide has been developed for the first time, which features a Cu-mediated amide coupling with vinyl iodide at the late stage. Other key transformations include Evans asymmetric alkylation, CBS asymmetric reduction, ring-closing metathesis reaction, and Stork-Zhao-Wittig olefination. This strategy is amenable for facile analogue preparation and SAR studies.