非经典紫杉烷二萜的化学,Accounts of Chemical Research

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非经典紫杉烷二萜的化学
Accounts of Chemical Research ( IF 16.4 ) Pub Date : 2021-05-04 , DOI: 10.1021/acs.accounts.0c00873
Fabian Schneider ₁ , Lu Pan ₁ , Moritz Ottenbruch ₁ , Tatjana List ₁ , Tanja Gaich ₁

Affiliation

紫杉烷二萜是药学上重要的天然产物家族，由 550 多种同源物组成。所有紫杉烷二萜均从生长缓慢的常绿灌木（红豆杉属）中分离出来，俗称“红豆杉”，作为有效的抗癌化合物已有 50 多年的历史。最突出的同类物紫杉醇（paclitaxel = PTX）已用于临床超过25年，是全球最畅销的抗癌药物之一，1999年年销售额达到15亿美元。紫杉烷二萜家族11已知源自“经典紫杉烷核心”的重排、断裂或跨环 C-C 键形成的不同支架。其中，仅五种不同的支架就属于所谓的复合物或环紫杉烷亚家族，它们的标志性结构特征在经典紫杉烷骨架上具有不同类型和数量的跨环 C-C 键。对于合成化学家来说，这五种支架是迄今为止最具挑战性的，因此避开了全合成和详细的药物评估——后者是由于从天然生产者那里采购的极其糟糕。复杂紫杉烷与紫杉醇的亲缘关系使它们成为抗癌药物研究中潜在的有趣化合物。

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The Chemistry of Nonclassical Taxane Diterpene

The taxane diterpenes are a pharmaceutically vital family of natural products, consisting of more than 550 congeners. All taxane diterpenes are isolated from slow growing evergreen shrubs (genus Taxus) commonly known as “yews” and have a history of over 50 years as potent anticancer compounds. The most prominent congener, taxol (paclitaxel = PTX), has been used in clinics for more than 25 years and is one of the top-selling anticancer drugs worldwide, with annual sales reaching 1.5 billion USD in 1999. Within the taxane diterpene family 11 different scaffolds originating from rearrangements, fragmentations, or transannular C–C bond formations of the “classical taxane core” are known. Among them, five different scaffolds alone belong to the so-called complex or cyclotaxane subfamily, their signature structural feature bearing different types and numbers of transannular C–C bonds across the classical taxane backbone. For synthetic chemists, these five scaffolds represent by far the most challenging of all and have thus evaded total synthesis as well as detailed pharmaceutical evaluation—the latter due to extremely poor sourcing from natural producers. The cousinship of complex taxanes to taxol renders them potentially interesting compounds for drug research in the fight against cancer.

更新日期：2021-05-18

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