Progress Towards the Total Synthesis of Nogalamycin using a Benzyne Cycloaddition Strategy

Nogalamycin (NOG) is a member of the anthracycline glycoside natural products; no total syntheses have yet been reported and there is minimal understanding of how the aglycone substitution pattern and the identities of the A- and D-ring sugar impact anticancer activity and toxicity. This paper reports progress towards a modular approach to NOG that could enable systematic structure-activity relationship studies. Key steps include a regioselective benzyne cycloaddition and a reductive ring-opening to assemble a versatile AB core for analogue synthesis.