拟天然产物化学进化研究进展

Research Progress in Chemical Evolution of Pseudo-natural Product

天然产物片段、生物合成中间体或化学性质活泼的天然产物是药物研发的重要资源。天然产物片段之间通过化学、非酶促或酶促等偶联反应组合产生骨架新颖、结构多样的拟天然产物,是天然产物人工化学进化的有效策略。这些拟天然产物可能具有片段不具备的新生物功能。拟天然产物策略产生的实体分子与上市的小分子药物、类药性分子化学空间重叠性高,更接近Lipinski规则,是药物发现的重要补充。综述阐明了近年拟天然产物化学进化策略在新颖分子创制及其新颖生物功能方面的进展。

Natural product fragments,biosynthetic intermediates,and chemo-reactive natural products are important resources for drug discovery.The combination of chemical,non-enzymatic or enzymatic coupling reaction between natural product fragments to produce novel skeletons and diverse pseudo-natural products is an effective strategy for the artificial chemical evolution of natural products.These pseudo-natural products may play novel biological functions not possessed by their fragments.The molecular entities generated by the pseudo-natural product-based strategy are similar to small molecule drugs and drug-like molecules,which is in line with Lipinski's rule,and so would be an important supplement for drug discovery.This review summarizes the recent progress in the strategy of pseudo-natural products-driven chemical evolution,focusing on the creation of novel molecules and their novel biological functions.