Synthesis of (±)-Idarubicinone via Global Functionalization of Tetracene
Synthesis of (±)-Idarubicinone via Global Functionalization of Tetracene
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DOI：
10.1021/jacs.9b05370
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发表时间：
2019-07-03
影响因子：
15
通讯作者：
Sarlah, David
中科院分区：
文献类型：
--
作者：
Dennis, David G.;Okumura, Mikiko;Sarlah, David
蒽环类是四环II型聚酮化合物天然产物的典型代表，广泛用于癌症化疗。虽然这类化合物的合成已经成为几项研究的主题，但所有已知的方法都是基于环化，依赖于适当预官能化的结构单元的结合。在这里，我们描述了一种概念上不同的方法，使用多核芳烃作为起始模板，理想情况下只需要功能性装饰，以达到所需的目标分子。具体地，通过Co-和Ru-催化的芳烃氧化和亲芳烃介导的脱芳硼氢化的明智协调，将并四苯转化为（+/-）-伊达比星酮，FDA批准的蒽环类伊达比星的糖苷配基。这种全局官能化策略，即位点选择性芳烃和脱芳香官能化的组合，在五个操作中提供了关键的蒽环类药物框架，并能够快速、受控地获得（+/-）-伊达比酮。
Anthracyclines are archetypal representatives of the tetracyclic type II polyketide natural products that are widely used in cancer chemotherapy. Although the synthesis of this class of compounds has been a subject of several investigations, all known approaches are based on annulations, relying on the union of properly prefunctionalized building blocks. Herein, we describe a conceptually different approach using a polynuclear arene as a starting template, ideally requiring only functional decorations to reach the desired target molecule. Specifically, tetracene was converted to (+/-)-idarubicinone, the aglycone of the FDA approved anthracycline idarubicin, through the judicious orchestration of Co- and Ru-catalyzed arene oxidation and arenophile-mediated dearomative hydroboration. Such a global functionalization strategy, the combination of site-selective arene and dearomative functionalization, provided the key anthracycline framework in five operations and enabled rapid and controlled access to (+/-)-idarubicinone.