6个上市的小分子海洋药物的全合成方法

The total synthesis method of six small molecular marine drugs

骨架新颖、活性独特的海洋天然产物是药物先导化合物的重要来源,但由于海洋样品采集困难、一些高活性天然产物在海洋生物体中含量低微,往往难以获取足够量的化合物进行后续药物的深入研究,成为海洋小分子药物研究的瓶颈之一。现代有机合成尤其是海洋天然产物全合成的迅猛发展,为获取复杂小分子海洋活性天然产物提供了1类重要手段。探究复杂小分子海洋天然产物合成的新策略和新方法,建立高效、高选择性的规模化制备技术,是国际海洋药物研究的热点。本文就6个上市的小分子海洋药物的全合成研究作一概述,重点阐述有机合成对于成药分子规模化制备的途径。

Marine derived natural products with novel skeleton and unique activity are important sources of leading compounds.However,it is difficult to collect marine samples and further the amount of high active compounds in marine organisms is usually scarce.These make it a challenge to obtain sufficient amount of compounds to conduct extensive druggability study.These problems become bottlenecks in small molecule marine drug research.The rapid development of modern organic synthesis,especially marine natural product total synthesis,provides an important approach to get access to complex small molecular marine bioactive natural products.Exploring new strategies and methods for complex small molecular or marine natural product synthesis and establishing efficient,highly selective and large-scale preparation technology have become a hot spot in world-wide marine drug research.In this perspective,we give an overview of the total synthesis of six small molecular marine drugs with the focus on the route of organic synthesis for large-scale preparation of products.