Oxidative cyclizations create many unique chemical structures that are characteristic of biologically active natural products. Many of these reactions are catalysed by ‘non-canonical’ or ‘thwarted’ iron oxygenases and appear to involve long-lived radicals. Mimicking these biosynthetic transformations with chemical equivalents has been a long-standing goal of synthetic chemists but the fleeting nature of radicals, particularly under oxidizing conditions, makes this challenging. Here we use redox-neutral photocatalysis to generate radicals that are likely to be involved in the biosynthesis of lignan natural products. We present the total syntheses of highly oxidized dibenzocyclooctadienes, which feature densely fused, polycyclic frameworks that originate from a common radical progenitor. We show that multiple factors control the fate of the proposed biosynthetic radicals, as they select between 5- or 11-membered ring cyclizations and a number of different terminating events. Our syntheses create new opportunities to explore the medicinal properties of these natural products, while shedding light on their biosynthetic origin.

氧化环化产生许多独特的化学结构，这些化学结构是具有生物活性的天然产物的特征。许多这些反应是由“非典型”或“受阻”的铁加氧酶催化的，并且似乎涉及长寿命的自由基。用化学等价物模拟这些生物合成转化一直是合成化学家的长期目标，但自由基的短暂性，特别是在氧化条件下，使这具有挑战性。在这里，我们使用氧化还原中性光催化产生可能参与木脂素天然产物生物合成的自由基。我们展示了高度氧化的二苯并环辛二烯的全合成，其特征在于源自共同自由基前体的密集稠合的多环框架。我们表明，多种因素控制了所提出的生物合成自由基的命运，因为它们在 5 或 11 元环环化和许多不同的终止事件之间进行选择。我们的合成为探索这些天然产品的药用特性创造了新的机会，同时揭示了它们的生物合成来源。