不对称的酶促化学合成（-）-鬼臼毒素和相关芳基四氢萘木脂素。
Asymmetric Chemoenzymatic Synthesis of (-)-Podophyllotoxin and Related Aryltetralin Lignans.
机构信息
Department of Chemistry, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL, 33458, USA.
出版信息
Angew Chem Int Ed Engl. 2019 Aug 19;58(34):11657-11660. doi: 10.1002/anie.201904102. Epub 2019 Jul 17.
Abstract
(-)-Podophyllotoxin is one of the most potent microtubule depolymerizing agents and has served as an important lead compound in antineoplastic drug discovery. Reported here is a short chemoenzymatic total synthesis of (-)-podophyllotoxin and related aryltetralin lignans. Vital to this approach is the use of an enzymatic oxidative C-C coupling reaction to construct the tetracyclic core of the natural product in a diastereoselective fashion. This strategy allows gram-scale access to (-)-deoxypodophyllotoxin and is readily adaptable to the preparation of related aryltetralin lignans.
摘要
(-)-鬼臼毒素是最有效的微管解聚剂之一，它是抗肿瘤药物发现中的一个重要先导化合物。本文报道了(-)-鬼臼毒素及相关芳基四氢萘木脂素的短路线酶促全合成。该方法的关键是利用酶促氧化 C-C 偶联反应以非对映选择性方式构建天然产物的四环核心。该策略允许(-)-脱氧鬼臼毒素进行克级规模的制备，并且易于适应相关芳基四氢萘木脂素的制备。
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