Stereodivergent total synthesis of Br-nannocystins underpinning the polyketide (10R,11S) configuration as a key determinant of potency

Abstract Continuing our investigation into the structure-activity relationship of antiproliferative macrocyclic nannocystins, we describe herein total synthesis of all four stereoisomers of Br-nannocystins as well as a simplified analogue varying at the polyketide C10 and C11 positions. Biological evaluation of these compounds against PANC1 cancer cell lines showed that both the (10 R ,11 S ) configuration and its associated two substituents are crucial for high potency.