噻唑/噁唑类活性天然产物及活性小分子化合物研究进展

Advances of studies in thiazole/oxazole-based bioactive natural products and small molecules

介绍了天然界中存在很多含有噻唑/噁唑结构单元的活性分子,其生物合成途径或仿生合成方法通常分别以多肽氨基酸残基的羧酸基团或羧酸衍生物为底物,与半胱氨酸/丝氨酸等天然氨基酸或经过衍生化的非天然氨基酸环合、氧化而成,因此天然产物中的噻唑/噁唑C5位通常以无取代的形式存在。然而,C5位二聚化、烯基化或芳基化的噻唑/唑结构单元常见于具有广泛药理活性的人工合成的分子中,构建这类结构单元通常都需预先制备β-取代的非天然氨基酸。并且,关于该类天然产物的结构改造均未涉及噻唑/噁唑C5位上的官能团化修饰,这是由于目前尚缺乏该位点上的官能团化方法而造成的。该现状预示着,开发噻唑/噁唑C5位官能团化新方法,并将其应用于噻唑/噁唑天然产物的结构修饰,具有十分重要的意义和研究价值。

Thiazole/oxazole moieties in natural or artificial bioactive compounds usually biologically or biomimetically synthesized through a coupling between carboxylic groups of amino acid residues or unnatural carboxylic derivatives and natural amino acids including cysteine and serine or other artificial amino acids, followed by an oxidation or dehydrogenation, which makes C5-functionalized thiazole/oxazole moieties very rare in natural bioactive molecules. On the contrary, these moieties have commonly been seen in artificial compounds with wide and potent pharmacological activities, yet synthesis of these artificial moieties requires preparation of ^- functionalized unnatural amino acids before the coupling and oxidation. In addition, CS- functionalizations of thiazole/oxazole-based natural products are also very rare, owing to the lack of related methodologies. These status suggest that discovering novel methodologies for the C5- functionalizations of thiazole/oxazole and applying them to the structural modification of tbiazole/ oxazole-based natural products will be extremely significant and valuable.