relationships in a straight-forward manner. This would enable systematic study of how the A-and D-ring sugars, as well as substitution on the aglycone core, impacts both the desirable and off-target activities. Our proposed retrosynthesis of NOG (Scheme 1) involves a threefragment convergent approach that couples the anthracycline core 2, the A-ring sugar (nogalose 3 in NOG) and a nogalamine aminosugar 4. The final step is inspired by the biosynthetic pathway, where native SnoK or an enzyme modified by directed evolution forges the challenging Caryl-Cglycoside bond in 1. While a bold strategy, postponing glycosylation until the penultimate steps allows greater flexibility for efficient analog preparation, where appending any accessible sugar or aminosugar to the aglycone can be explored.