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

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 (10R,11S) configuration and its associated two substituents are crucial for high potency.