Bysspectin A (1), an unusual polyketide-derived octaketide dimer, has highly selective inhibitory activities against human carboxylesterase 2 (hCE2) with an IC50 value of 2.01 mu M. Herein, we report the first synthesis of this natural product. The synthesis relies upon a key Cu-catalysed domino Sonogashira-cyclization process. (C) 2019 Elsevier Ltd. All rights reserved.