The importance of macrocyclic peptides in drug discovery has spawned a variety of modern techniques to improve their synthesis. Although photocatalysis is now an indispensable tool in the synthesis of natural products and pharmaceuticals, it is rarely exploited in macrocyclization. Photochemical macrocyclization remains rare and is hampered by challenges in efficiency and scale-up. A “hybrid” reactor that incorporates aspects of plug flow and continuously stirred tank reactor systems is reported, which allows for slow addition strategies typically associated with batch processes. Via efficient light penetration, mixing, and gas manipulation, a macrocyclic aerobic oxidative coupling of thiols employing low catalyst loadings (1 mol %) was developed to access a variety of peptidic macrocycles on preparative scales. Preparation of “macromulticycles” was also demonstrated. The hybrid reactor outperformed existing technologies and permitted rare gram-scale photochemical macrocyclization.

中文翻译：

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肽光化学大环化的流动化学平台

大环肽在药物发现中的重要性催生了多种现代技术来改进其合成。尽管光催化现在是天然产物和药物合成中不可或缺的工具，但在大环化中却很少被利用。光化学大环化仍然很少见，并且受到效率和规模化挑战的阻碍。据报道，一种“混合”反应器结合了活塞流和连续搅拌釜反应器系统的各个方面，它允许通常与间歇过程相关的缓慢添加策略。通过有效的光穿透、混合和气体操纵，开发了采用低催化剂负载量（1 mol%）的硫醇大环有氧氧化偶联，以在制备规模上获得各种肽大环化合物。还演示了“宏观多循环”的制备。该混合反应器的性能优于现有技术，并允许罕见的克级光化学大环化反应。